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GIUSEPPE TORELLI
Professore emerito
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
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Pubblicazioni
- Metodo per la diagnosi e/o il monitoraggio dell’ aspergillosi invasiva
[Brevetto]
Torelli, Giuseppe; Luppi, Mario; Barozzi, Patrizia; Potenza, Leonardo
abstract
La presente invenzione si riferisce ad un metodo per la diagnosi e/o ilmonitoraggio dell’infezione attiva o pregressa da Aspergillus fumigatus checomprende l’esecuzione di un saggio immunoenzimatico in vitro (ELISPOT) incui il campione da fluidi biologici prelevato dal paziente è messo in contatto conun antigene di Aspergillus fumigatus.
2012
- Physical contact with endothelial cells through β1- and β2- integrins rescues chronic lymphocytic leukemia from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile on leukemic cells.
[Articolo su rivista]
Maffei, Rossana; Fiorcari, Stefania; Bulgarelli, Jenny; Martinelli, Silvia; Castelli, Ilaria; Deaglio, S; Debbia, Giulia; Fontana, M; Coluccio, Valeria; Bonacorsi, G; Zucchini, Patrizia; Narni, Franco; Torelli, Giuseppe; Luppi, Mario; Marasca, Roberto
abstract
Background: Chronic lymphocytic leukemia B-cells display prolonged survival in vivo, but when cultured in vitro rapidly undergo spontaneous apoptosis. We hypothesize that interaction with endothelial cells in infiltrated tissues and during recirculation may have a pathogenetic role in chronic lymphocytic leukemia.Design and Methods: We evaluated apoptosis of leukemic cells after co-culture on HUVEC monolayer with addition of Fludarabine and blocking adhesion antibodies. Then, we compared microarray-based expression profiles between leukemic cells at baseline and after co-culture.ùResults: We found that endothelial layer protected leukemic cells from apoptosis inducing a 2-fold mean decrement in apoptotic cells after 2 days co-culture. Moreover, endothelial layer decreased sensitivity of chronic lymphocytic leukemia B-cells to Fludarabine-induced apoptosis. Physical contact with endothelium mediated by both β1- and β2- integrins is essential for survival advantage. In particular, blocking CD106 on endothelial cells or CD18 on leukemic B-cells determined the almost complete abrogation of survival advantage (>70% inhibition of viability). Conversely, a reduction of apoptosis was also measured in leukemic cells cultured in conditioned medium collected after 2 days of co-culture, implying that survival is partially mediated by soluble factors. Overall, the contact with endothelial cells modulated 1,944 genes on chronic lymphocytic leukemia B-cells, establishing a peculiar gene expression profile: up-regulation of angiogenesis-related genes, increase of genes involved in TGFβ and Wnt signalling pathways, secretion of cytokines recruiting stromal cells and macrophages and increase in anti-apoptotic molecules such as Bcl2 and Survivin. Conclusion: Our study supports the notion that endothelial cells are major players in chronic lymphocytic leukemia microenvironment. Adhesion to endothelium strongly sustains survival, protects from drug-induced apoptosis and widely modifies gene expression profile of leukemic cells.
2011
- A case of JAK2 V617F-positive myelodysplastic/myeloproliferative neoplasm with unusual morphology, resembling acute promyelocytic leukemia-like disorder with a chronic course.
[Articolo su rivista]
Forghieri, Fabio; Morselli, M; Potenza, Leonardo; Maccaferri, Monica; Pedrazzi, Letizia; Coluccio, Valeria; Barozzi, Patrizia; Vallerini, Daniela; Riva, Giovanni; Zanetti, Eleonora; Quarelli, C; Bonacorsi, G; Artusi, Tullio; Zaldini, Piera; Zucchini, Patrizia; Marasca, Roberto; Narni, Franco; Falini, B; Torelli, Giuseppe; Luppi, Mario
abstract
An atypical case of myelodysplastic syndrome with morphologic aspect resempling acute promyelocytic leukemia, carring JA2 mutations.
2011
- Chronic eosinophilic leukaemia with ETV6-NTRK3 fusion transcript in an elderly patient affected with pancreatic carcinoma
[Articolo su rivista]
Forghieri, Fabio; Morselli, M; Potenza, Leonardo; Maccaferri, Monica; Pedrazzi, Letizia; Paolini, Ambra; Bonacorsi, G; Artusi, Tullio; Giacobbi, F; Corradini, G; Barozzi, Patrizia; Zucchini, Patrizia; Marasca, Roberto; Narni, Franco; Crescenzi, B; Mecucci, C; Falini, B; Torelli, Giuseppe; Luppi, Mario
abstract
Chronic eosinophilic leukaemia with ETV6-NTRK3 fusion transcript in an elderly patient affected with pancreatic carcinoma.A case report
2011
- INTERACTION BETWEEN ENDOTHELIUM AND CHRONIC LYMPHOCYTIC LEUKEMIA B-CELLS RESCUES FROM APOPTOSIS AND MODULATES GENE EXPRESSION PROFILE OF LEUKEMIC CELLS
[Abstract in Rivista]
Maffei, Rossana; Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Debbia, Giulia; Fontana, M; Faglioni, Laura; Bigliardi, Sara; Zucchini, Patrizia; Narni, Franco; Torelli, Giuseppe; Luppi, Mario; Marasca, Roberto
abstract
Background. Despite an apparent long life in vivo, CLL cells die rap-
idly in vitro. This observation suggests that the apoptotic resistance is
not intrinsic to leukemia B cells but extrinsic factors are necessary for
CLL prolonged survival. Aims. we investigated the interactions be-
tween endothelial cells and CLL cells, highlighting molecular net-
works involved in this cellular crosstalk. Methods. we co-cultured CLL
cells on HUVEC endothelial monolayer (HC) or in medium alone
(CLL only). Then, we detected CLL viability by flow cytometry and
we performed whole-genome high density microarrays. Results. we
found that endothelial cells protected CLL from spontaneous apop-
tosis. After 48h, increased number of alive CLL cells was present in
HC condition (59.7 ± 4.2%) compared to CLL alone (22.9 ± 5.1%)
(p<0.0001). Moreover, we found that spontaneous in vitro apoptosis
was higher in unmutated IGHV CLL (UM-CLL) compared to mutated
ones (M-CLL). In HC condition, similar survival was detected be-
tween M-CLL and UM-CLL, implying a 2.2-fold increase in relative
viability in M-CLL and a 6.1-fold increase in UM-CLL. Moreover, the
endothelial cell layer decreased the in vitro sensitivity of CLL cells to
Fludarabine-induced apoptotic cell death. The mean viability of CLL
cells treated with 10 µM Fludarabine was 19.8% (±4.4%) after 48
hours and 3.8% (±1.3%) after 72 hours. In HC with Fludarabine ad-
dition, the mean viability of CLL cells was 37.8% (±9.1%) after 48
hours and 14.3% (±3.2%) after 72 hours. Then, we compared gene
expression profiles (GEP) between CLL cultured in contact with EC
layer and CLL at baseline to unravel the transcriptional modifications
induced by EC cells. Overall 1944 genes were found to be modulated
(FC≥2, p<0.05). CLL cells in HC condition showed a 22.6-fold in-
crease of CCL2, able to recruit tumor-activated monocytes
(p=0.0032) and a 6.5-fold increase of PDGFC, chemoattractant for
mesenchymal stromal cells (p=0.0051). Other soluble factors up-reg-
ulated by EC/CLL contact were VEGFC (FC=9.4, p=0.0061),
ANGTL4 (FC=8.6, p=0.015), EDN1 (FC=9.2, p=0.0061), AMOTL2
(FC=4.3, p=0.019) and THBS1 (FC=45.1, p=0.0004) as well as the
metalloproteases MMP2 (FC=8.3, p=0.02) and MMP4 (FC=3.0,
p=0.039). The GEP data were confirmed by evaluating the secreted
levels of soluble factors in conditioned medium collected after 48h-
HC culture. In addition, CLL cells on endothelial layer maintained or
increased the expression levels of anti-apoptotic factors Bcl-2,
Bcl2A1, BIRC3/c-IAP2 and BIRC5/Survivin compared to CLL cells at
baseline. Of interest, the Ang2 tyrosine kinase receptor Tie2 mRNA
was found to be increased in CLL cells in co-culture (FC=10.7,
p=0.017). We confirmed GEP data by flow cytometry finding a 2-fold
and a 4.3-fold increase of percentage of Tie2+CLL cells at 48h and
72h in HC. Conclusion. our results demonstrate a role of endothelial
cells in CLL survival advantage and Fludarabine-resistance. The inti-
mate contacts with EC seem to determine a microenvironmental-
driven angiogenic switch of CLL phenotype, improve the secretion of
cytokines involved in regulation of microenvironmental elements
such as stromal cells and macrophages and increase the expression of
anti-apoptotic molecules.
2010
- Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.
[Articolo su rivista]
Maffei, Rossana; Martinelli, Silvia; Santachiara, R; Rossi, D; Guarnotta, C; Sozzi, E; Zucchetto, A; Rigolin, Gm; Fiorcari, Stefania; Castelli, Ilaria; Fontana, M; Coluccio, Valeria; Leonardi, G; Zucchini, P; Tripodo, C; Cuneo, A; Gattei, V; Del Poeta, G; Forconi, F; Gaidano, G; Torelli, Giuseppe; Marasca, Roberto
abstract
The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high beta(2)-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and zeta-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.
2010
- Cytogenetic abnormalities and clinical features in a patient cohort affected by three or more synchronous or metachronous primitive malignancies.
[Articolo su rivista]
Ponti, Giovanni; Luppi, G; Giacobbi, F; Corradini, G; Temperani, Paola; Losi, Lorena; Ferrara, L; Pagano, M; Seidenari, Stefania; Tagliafico, Enrico; Torelli, Giuseppe; Conte, Pierfranco
abstract
The multiple cancers (MC) phenotype represents an intriguing entity from both the clinical and the biomolecular points of view. Multiple cancers can arise in a patient either synchronously or metachronously and are frequently detected in hereditary disorders. Here we report the clinical and cytogenetic characterization of 48 patients developing at least three malignancies outside the context of a known genetic condition and 30 control individuals. Medical and pathology reports were registered, blood was collected for cytogenetic studies, and the standard G-banding technique was used for chromosomal analysis of the lymphocyte cultures. Chromosomal analysis of the peripheral blood cultures revealed high cytogenetic instability in 83% of patients' karyotypes that displayed structural rearrangements most often involving chromosomes X, 1, 6, and 7. Peculiar telomeric associations and marker chromosomes were detected in patients with a suspected cancer family history. The MC condition can be observed over a wide clinical range, which includes either apparently sporadic cases or families with a strong history of tumors. These findings indicate that Xq, 6p, and 7q are likely to harbor genes of importance in cancer development, and the present cytogenetic mapping may be crucial for further molecular genetic investigations to recognize a predictive cytogenetic signature useful to detect patients with a high risk of multiple malignancies.
2010
- Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term Imatinib mesylate treatment.
[Articolo su rivista]
Riva, Giovanni; Luppi, Mario; Barozzi, Patrizia; Quadrelli, Chiara; Basso, S; Vallerini, Daniela; Zanetti, Eleonora; Morselli, M; Forghieri, Fabio; Maccaferri, M; Volzone, F; DEL GIOVANE, Cinzia; D'Amico, Roberto; Locatelli, F; Torelli, Giuseppe; Comoli, P; Potenza, Leonardo
abstract
Imatinib mesylate (IM) has been demonstrated to be permissive for the emergence of T cells directed against chronic myeloid leukemia cells. Ten Philadelphia chromosome-positive acute lymphoblastic leukemia patients, receiving high dose IM maintenance, underwent a long-term immunological monitoring (range 2-65 months) of (p190)BCR-ABL-specific T cells in the bone marrow (BM) and peripheral blood (PB). (p190)BCR-ABL-specific T lymphocytes were detected in all patients, more frequently in BM than in PB samples (67% vs 25%, p<0.01), and resulted significantly associated with lower minimal residual disease values (p<0.001), while absent at leukemia relapse. Specific T cells were mainly effector memory CD8+ and CD4+ T cells, producing IFNgamma, TNFalpha and IL-2 (median % positive cells: 3.34, 3.04, 3.58, respectively). Cytotoxic subsets able to lyse BCR-ABL-positive leukemia blasts were also detectable. Whether these autologous (p190)BCR-ABL-specific T cells may be detectable under other tyrosine-kinase inhibitors, expanded ex vivo and exploited for immunotherapy remains to be addressed.
2010
- HHV-6 and atypical lymphoproliferative disorders: are only qualitative molecular examinations sufficient to support a pathogenetic role?
[Articolo su rivista]
Forghieri, Fabio; Potenza, Leonardo; Barozzi, Patrizia; Vallerini, Daniela; Riva, Giovanni; Zanetti, Eleonora; Quadrelli, Chiara; Torelli, Giuseppe; Luppi, Mario
abstract
n.d.
2010
- Immunological and inflammatory features of Kaposi's sarcoma and other Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8-associated neoplasias.
[Articolo su rivista]
Riva, Giovanni; Barozzi, Patrizia; Torelli, Giuseppe; Luppi, Mario
abstract
During the last 15 years, virologic and immunologic studies have provided a series of valuable clues on the modalities of gamma-herpesvirus-induced oncogenesis, which do not only consist of the direct subversion of intracellular signaling pathways, leading to a frank neoplastic molecular network in the infected cell, but also rely on viral manipulations of the cellular and cytokine microenvironment, especially in conditions of immunodeficiency in the host. At the virus-host interface, something iniquitous, strikingly favoring the aggressive expansion of human herpesvirus 8-infected lympho-endothelial clones, known as Kaposi's sarcoma, often occurs in different types of immunocompromised patients, able to establish a deleterious "pro-Kaposi's sarcoma" neo-angiogenic inflammatory network. However, these patients may control - or even resolve - the neoplastic burden as soon as an immunologic reassessment restores functional anti-Kaposi's sarcoma immune responses and reconstitutes a proper inflammatory environment. Indeed, the occurrence of iatrogenic Kaposi's sarcoma remissions, after the reduction or switch of immunosuppressive regimens, strongly suggests that the reset of immunologic constraints characterizing the Kaposi's sarcoma onco-pathogenic system may be sufficient to inhibit human herpesvirus 8-positive lympho-endothelial proliferations. Accordingly, immunologic reports all underline the pivotal protective role of anti-human herpesvirus 8 memory T-cells (harmonically, both CD8+ and CD4+ subsets), thus definitely implying a general requirement for an effective, antiviral immuno-inflammatory environment, based on correct and productive interactions between different compartments of dendritic, myeloid, and specific T-cells, in order to achieve and maintain optimal control on human herpesvirus 8-associated antigenic stimulations and Kaposi's sarcoma disease. In this review, we recapitulate some remarkable features about the outstanding immunologic issue raised by human herpesvirus 8-driven neoplastic outgrowths in immunodeficient patients, and in particular, we discuss the emerging view of Kaposi's sarcoma as an atypical neoplastic process, tightly dependent on immune system dynamics. It is conceivable that functional dissection of the specific immune responses, capable to cope with human herpesvirus 8, and further definitions of a global inflammatory profile with protective activity against Kaposi's sarcoma outbreaks, will eventually foster immunologic monitoring protocols during the follow-up of AIDS and posttransplant patients, either preventing or treating human herpesvirus 8-related tumors by multifunctional immunomodulation or prompt development of adoptive immunotherapeutic approaches.
2010
- Increased angiogenesis induced by chronic lymphocytic leukemia B cells is mediated by leukemia-derived Ang2 and VEGF.
[Articolo su rivista]
Maffei, Rossana; Martinelli, Silvia; Castelli, Ilaria; Santachiara, R; Zucchini, Patrizia; Fontana, M; Fiorcari, Stefania; Bonacorsi, G; Ilariucci, F; Torelli, Giuseppe; Marasca, Roberto
abstract
Emerging evidence suggests that angiogenic signalling pathways play important role in the patho-biology of chronic lymphocytic leukemia (CLL). Our goal was to investigate: (i) the spontaneous and hypoxia-induced production of pro-angiogenic factors, VEGF and Ang2, by Real-time PCR and ELISA, (ii) the degree of vascularization in CLL-infiltrated bone marrow (BM) compartment by CD34 immunohistochemical staining of microvessels and (iii) the direct angiogenic effect of CLL-derived VEGF and Ang2 by function-blocking experiments in Matrigel assays. The results demonstrated that CLL cells spontaneously express both VEGF and Ang2 and are able to secrete these factors in surrounding microenvironment. Full-length Ang2 mRNA and truncated form Ang2443 were detectable. Moreover, CLL cells were shown to enhance secretion of both VEGF and Ang2 proteins when subjected to hypoxic condition. Furthermore, increased in vivo and in vitro angiogenesis was induced by CLL cells. Enhanced BM vascularity correlated with Ig-unmutated CLL subset and increased expression of Ang2. Then, we demonstrated that supernatants obtained from CLL cells significantly increase the HUVEC tube formation in Matrigel assays and that this enhanced angiogenic capacity is mediated by both CLL-derived VEGF and Ang2. Taken together, these results suggest that several simultaneous mechanisms may be involved in the CLL capacity to induce the disruption of pre-existing vessel structures to give rise to tumor neoangiogenesis. The preliminary studies in solid tumors, showing that the disruption of Ang2 function can inhibit tumor vessel density and growth, are encouraging and suggest the possibility of new future therapeutic options targeting CLL microenvironment.
2010
- Organising pneumonia mimicking invasive fungal disease in patients with leukaemia.
[Articolo su rivista]
Forghieri, Fabio; Potenza, Leonardo; Morselli, M; Maccaferri, Monica; Pedrazzi, L; Barozzi, Patrizia; Vallerini, Daniela; Riva, Giovanni; Zanetti, Eleonora; Quadrelli, Chiara; Rossi, G; Rivasi, Francesco; Messino', M; Rumpianesi, F; Grottola, Antonella; Venturelli, C; Pecorari, M; Codeluppi, M; Torelli, Giuseppe; Luppi, Mario
abstract
Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.
2010
- Pain and emotional distress in leukemia patients at diagnosis.
[Articolo su rivista]
Morselli, M; Bandieri, E; Zanin, R; Buonaccorso, L; D'Amico, Roberto; Forghieri, Fabio; Pietramaggiori, A; Potenza, Leonardo; Berti, A; Cacciapaglia, G; Molitierno, A; Galli, L; Artioli, F; Ripamonti, C; Bruera, E; Torelli, Giuseppe; Luppi, Mario
abstract
Pain and emotional distress in leukemia patients at diagnosis.
2010
- Pregnancy in PNH: another eculizumab baby.
[Articolo su rivista]
Marasca, Roberto; Coluccio, Valeria; Santachiara, R; Leonardi, G; Torelli, Giuseppe; Notaro, R; Luzzatto, L.
abstract
Pregnancy in PNH: another eculizumab baby.
2010
- Splenic hyalohyphomycosis, molecularly and immunologically consistent with invasive aspergillosis, in a patient with acute lymphoblastic leukemia.
[Articolo su rivista]
Forghieri, Fabio; Rossi, G; Potenza, Leonardo; Morselli, M; Barozzi, Patrizia; Vallerini, Daniela; Messino, M; Rumpianesi, F; Pecorari, M; Torelli, Giuseppe; Luppi, Mario
abstract
n.d.
2009
- Acute promyelocytic leukemia in very elderly patients: still aclinical challenge.
[Articolo su rivista]
Forghieri, Fabio; Luppi, Mario; Morselli, M; Favale, V; Potenza, Leonardo; Volzone, F; Maccaferrim, ; Torelli, Giuseppe
abstract
n.d.
2009
- Diagnosis of aspergillosis: Role of proteomics
[Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Vallerini, Daniela; Zanetti, Eleonora; Torelli, Giuseppe; Luppi, Mario
abstract
The expansion of the antifungal armamentarium and the implementation of imaging techniques and new nonculture-based fungal diagnostics (NCBFDs) have improved the survival of patients with invasive aspergillosis (IA). However, mortality rates still remain high, possibly influenced by several pitfalls, affecting NCBFDs and reducing the window of opportunity for earlier treatment. A large body of in vitro and in vivo studies has demonstrated that several fungal proteic components are strongly immunogenic, and both the adaptive immunity and the innate branch are heavily involved in the recognition and clearance of fungal pathogens, resulting, on occasion, in a useful tool for the treatment of IA. By evaluating these studies, this review considers the possibility of exploiting either components of the innate or adaptive immunity to support the rapid and early diagnosis of IA. Copyright © 2009 by Current Medicine Group LLC.
2009
- Indirect Antitumor Effects of Mammalian Target of Rapamycin Inhibitors Against Kaposi Sarcoma in Transplant Patients
[Articolo su rivista]
Barozzi, Patrizia; Riva, Giovanni; Vallerini, Daniela; Bosco, Raffaella; Quadrelli, Chiara; Zanetti, Eleonora; Potenza, Leonardo; Forghieri, Fabio; Torelli, Giuseppe; Luppi, Mario
abstract
n.d.
2009
- Inflammatory myofibroblastic tumor of the bone marrow.
[Articolo su rivista]
Saviola, Alessia; Rossi, Giulio; Bonacorsi, G; Forghieri, Fabio; Fiorani, C; Artusi, Tullio; Emilia, Giovanni; Luppi, Mario; Longo, G; Torelli, Giuseppe
abstract
n.d.
2009
- Interferon-alpha may restore sensitivity to tyrosine-kinase inhibitors in Philadelphia chromosome positive acute lymphoblastic leukaemia with F317L mutation
[Articolo su rivista]
Potenza, Leonardo; Volzone, F; Riva, Giovanni; Soverini, S; Martinelli, S; Iacobucci, I; Gnani, A; Barozzi, Patrizia; Forghieri, Fabio; Morselli, M; Zanetti, E; Maccaferri, Monica; Baccarani, M; Martinelli, G; Torelli, Giuseppe; Luppi, Mario
abstract
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2009
- Persistent hiccups as an adverse event to FLAG-IDA regimenfor leukemia.
[Articolo su rivista]
Forghieri, Fabio; Maccaferri, M; Morselli, M; Potenza, Leonardo; Volzone, F; Bandieri, E; Torelli, Giuseppe; Luppi, Mario
abstract
n.d.
2009
- Prevalence of Human Herpesvirus-6 Chromosomal Integration (CIHHV-6) in Italian Solid Organ and Allogeneic Stem Cell Transplant Patients
[Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Masetti, M; Pecorari, M; Bresciani, P; Gautheret Dejean, A; Riva, Giovanni; Vallerini, Daniela; Tagliazucchi, S; Codeluppi, M; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico; Narni, Franco; Torelli, Giuseppe; Luppi, Mario
abstract
The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6.
2008
- A possible role for low-dose cyclosporine in refractory immune thrombocytopenic purpura.
[Articolo su rivista]
Emilia, Giovanni; Luppi, Mario; Morselli, M; Forghieri, F; Potenza, Leonardo; Torelli, Giuseppe
abstract
n.d.
2008
- Acute appendicitis in adult neutropenic patients with hematologic malignancies
[Articolo su rivista]
Forghieri, Fabio; Luppi, Mario; Narni, Franco; Morselli, M.; Potenza, Leonardo; Bresciani, Paola; Volzone, Francesco; Rossi, Giulio; Rossi, Aldo; Trenti, Loris; Barozzi, Patrizia; Torelli, Giuseppe
abstract
n.d.
2008
- Assessment of aspergillus-specific T cells for diagnosis of invasive aspergillosis in a leukemic child with liver lesions mimicking hepatosplenic candidiasis
[Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Rossi, Giulio; Palazzi, G; Vallerini, Daniela; Riva, Giovanni; Cellini, M; Morselli, M; Volzone, Francesco; Venturelli, C; Quadrelli, Chiara; Di Pancrazio, L; Cano, Mc; Paolucci, Paolo; Torelli, Giuseppe; Luppi, Mario
abstract
A child with acute myeloid leukemia presented with multiple liver lesions mimicking hepatosplenic candidiasis during the neutropenic phase following the induction chemotherapy. All the available diagnostic tools showed repeatedly negative results, including galactomannan. An enzyme-linked immunospot (ELISPOT) assay showed a high number of Aspergillus-specific T cells producing interleukin-10 [TH2(IL-10)] and a low number of Aspergillus-specific T cells producing gamma interferon [TH1(IFN-γ)], revealing invasive aspergillosis (IA) before the confirmatory biopsy. A progressive skewing from the predominance of TH2(IL-10) to a predominance of TH1(IFN-γ) was observed close to the complete resolution of the infection and foreshadowed the outcome. The ELISPOT assay holds promise for diagnosing pediatric IA.
2008
- BK virus infection and neurologic dysfunctions in a patient with lymphoma treated with chemotherapy and rituximab
[Articolo su rivista]
Ferrari, A; Luppi, Mario; Marasca, Roberto; Potenza, Leonardo; Morselli, M; Volzone, F; Santachiara, R; Forghieri, Fabio; Barozzi, Patrizia; Torelli, Giuseppe
abstract
n.d.
2008
- Changes in the immune responses against human herpesvirus-8 in the disease course of posttransplant Kaposi sarcoma
[Articolo su rivista]
Barozzi, Patrizia; Bonini, C; Potenza, Leonardo; Masetti, Michele; Cappelli, Gianni; Gruarin, P; Whitby, D; Gerunda, Giorgio Enrico; Mondino, A; Riva, Giovanni; Vallerini, Daniela; Quadrelli, Chiara; Bosco, Raffaella; Ciceri, F; Bordignon, C; Schulz, Tf; Torelli, Giuseppe; Luppi, Mario
abstract
In nine patients with posttransplant Kaposi sarcoma (KS) T-cell responses to human herpesvirus (HHV)-8 latent and lytic antigens, as detected by enzyme-linked-immunospot (Elispot) assay, were absent at disease onset. Virus-specific T-cell responses were detected in six renal recipients at remission after a reduction of calcineurin inhibitors (CIs), and in two HHV-8 seropositive renal recipients without KS. In two liver recipients undergoing switch from CIs to sirolimus (SRL), normalization of the T-cell repertoire and recovery of both HHV-8-specific effector and memory T lymphocytes were associated with complete KS remission. In a renal recipient undergoing SRL conversion, the early recovery of HHV-8-specific effector but not of memory T lymphocytes, was associated only with partial remission. Neither rejection nor changes in graft function were observed after SRL conversion. HHV-8-specific T-cell responses are required to achieve posttransplant KS remission, and may be restored under SRL, while maintaining effective immunosuppression.
2008
- Development of hypogammaglobulinemia in patients treated with imatinib for chronic myeloid leukemia or gastrointestinal stromal tumor
[Articolo su rivista]
Santachiara, Rita; Maffei, Rossana; Martinelli, Silvia; Arcari, Annalisa; Piacentini, Federico; Trabacchi, Elena; Alfieri, Pierluigi; Ferrari, Angela; Leonardi, Giovanna; Luppi, Gabriele; Longo, Giuseppe; Vallisa, Daniele; Marasca, Roberto; Torelli, Giuseppe
abstract
Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukemia and gastrointestinal stromal tumor patients. Although several in vitro and animal studies demonstrated that imatinib affects immune response, few immune alterations are described in humans. We retrospectively studied hematologic and immunological parameters in 72 chronic myeloid leukemia and 15 gastrointestinal stromal tumor patients treated with imatinib at standard dosage and in 20 chronic myeloid leukemia patients treated before the introduction of imatinib in clinical practice. Both chronic myeloid leukemia and gastrointestinal stromal tumor patients developed a significant reduction of gammaglobulin and immunoglobulin serum levels. No significant hypogammaglobulinemia was observed in chronic myeloid leukemia patients in the pre-imatinib era. These data demonstrate that imatinib treatment induces hypogammaglobulinemia that can reach a severe entity in 10% of cases, both in chronic myeloid leukemia and in gastrointestinal stromal tumor patients. Prospective studies are needed to evaluate immune humoral alterations and to define the real incidence of infectious events, including viral reactivations.
2008
- HHV-6A in syncytial giant-cell hepatitis
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Barozzi, Patrizia; Rossi, Giulio; Cocchi, Stefania; Codeluppi, Mauro; Pecorari, Monica; Masetti, Michele; DI BENEDETTO, Fabrizio; Gennari, William; Portolani, Marinella; Gerunda, Giorgio Enrico; Lazzarotto, Tiziana; Landini, Maria Paola; Schulz, Thomas F.; Torelli, Giuseppe; Guaraldi, Giovanni
abstract
Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.
2008
- Increased expression of angiopoietin-2 characterizes early B-cell chronic lymphocytic leukemia with poor prognosis
[Articolo su rivista]
Martinelli, Silvia; Maffei, Rossana; Castelli, Ilaria; Santachiara, R; Zucchini, Patrizia; Fontana, M; Bonacorsi, G; Leonardi, G; Marasca, Roberto; Torelli, Giuseppe
abstract
We measured the angiopoietin-2 (Ang-2) expression in early chronic lymphocytic leukemia (CLL) patients, pointing our attention on the association with immunoglobulin (IgVH) mutational status, CD38 expression and clinical outcome. Our results indicate that Ang-2 expression is heterogeneous among Binet stage A CLL patients. CLL patients can be divided into two subgroups (Ang-2 positive and Ang-2 negative CLL) with 30% of them displaying Ang-2 RNA levels above the cut off. A shorter progression-free survival was observed in Ang-2 positive CLL subset (p = 0.032). Abnormal Ang-2 expression was also associated with unmutated IgVH genes (p < 0.0001) and increased bone marrow angiogenesis (p = 0.028), suggesting a role of Ang-2 in disease-progression of early CLL patients.
2008
- Parvoviruses in blood donors and transplant patients, Italy
[Articolo su rivista]
Vallerini, Daniela; Barozzi, Patrizia; Quadrelli, Chiara; Bosco, Raffaella; Potenza, Leonardo; Riva, Giovanni; Gregorini, G; Sandrini, S; Tironi, A; Montagnani, Giuliano; De Palma, M; Torelli, Giuseppe; Delwart, E; Luppi, Mario
abstract
n.d.
2008
- Veicolazione liposomiale del cidofovir nel trattamento del PEL (Primary Effusion Lynphoma)
[Abstract in Rivista]
Barozzi, Patrizia; Riva, Giovanni; Ruozi, Barbara; Tosi, Giovanni; Belletti, Daniela; Potenza, Leonardo; Quadrelli, Chiara; Vallerini, Daniela; Zanetti, Eleonora; M., Morselli; Forghieri, Fabio; Maccaferri, Monica; A., Paolini; F., Volzone; Vandelli, Maria Angela; Forni, Flavio; Torelli, Giuseppe; Luppi, Mario
abstract
Veicolazione liposomiale del cidofovir nel trattamento del PEL (Primary Effusion Lynphoma)
2007
- Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status
[Articolo su rivista]
Maffei, Rossana; Marasca, Roberto; Martinelli, Silvia; Castelli, Ilaria; Santachiara, R; Morandi, E; Zucchini, Patrizia; Fontana, M; Giacobbi, F; Silingardi, P; Bonacorsi, G; Temperani, Paola; Masini, L; Colacci, Am; Serra, Roberto; Torelli, Giuseppe
abstract
Chronic lymphocytic leukemia (CLL) has been considered for several years a disease of accumulation of relentless mature-looking malignant monoclonal B cells due to a presumeddefect in programmed cell death. However, several observations suggest that CLL cells are not immortal and that they require signals from microenvironment to maintain viability. Increased microvessel density in marrow and lymph node and increased levels of certain proangiogenetic factors in blood and urine of CLL patients were observed.2 Angiopoietin-2 (Ang-2) has a pivotal role in the disruption of stability and quiescence of mature vasculature that coincides with the reinitiation of vascular remodelling and angiogenic sprouting in adult, as occurs in tumors.
2007
- B cells and herpesviruses: a model of lymphoproliferation
[Articolo su rivista]
Barozzi, Patrizia; Potenza, Leonardo; Riva, Giovanni; Vallerini, Daniela; Quadrelli, Chiara; Bosco, Raffaella; Forghieri, Fabio; Torelli, Giuseppe; Luppi, Mario
abstract
Unlike alpha- and beta-herpesviruses, human gamma-herpesviruses, including the Epstein-Barr virus (EBV) and the human herpesvirus-8 (HHV-8), are B lymphotropic viruses. Primary infection with EBV, in otherwise healthy subjects, causes a benign lymphoproliferative syndrome, the mononucleosis syndrome. However, several epidemiologic and biologic studies have shown a pathogenetic role of EBV in the development of human B cell lymphomas, both in immunocompetent and in immunosuppressed individuals. HHV-8 is the necessary etiologic agent of a lymph vascular tumor, the Kaposi sarcoma, but it is also implicated in the pathogenesis of rare B cell lymphoproliferative disorders, mainly occurring in the setting of immunosuppression. The aim of this review is to provide an updated description of the different strategies used by these two herpesviruses to influence B cell fate decisions. Both EBV and HHV-8 have evolved specific mechanisms in order to: (1) interact with the B cell developmental machinery; (2) allow infected B cells to escape from the control of the immune system; (3) affect the B cell cycle checkpoints; (4) mimic and influence B cellular proliferation and differentiation pathways. Understanding the mechanisms of herpesvirus induced B cell lymphoproliferation will provide the basis for novel treatment approaches in patients with EBV and HHV-8 related lymphomas.
2007
- Diagnosis of invasive aspergillosis by tracking Aspergillus-specific T cells in hematologic patients with pulmonary infiltrates
[Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Vallerini, Daniela; Bosco, R; Quadrelli, Chiara; Morselli, M; Forghieri, Fabio; Volzone, F; Codeluppi, M; Rossi, G; Tazzioli, Giovanni; Venturelli, C; Torelli, Giuseppe; Luppi, Mario; Mediani, Laura
abstract
n.d.
2007
- Epstein-Barr virusassociated pneumonia in an adult patient with severe aplastic anaemia: resolutionafter the transient withdrawal of cyclosporine.
[Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Codeluppi, M; Morselli, M; Forghieri, Fabio; Volzone, F; Riva, Giovanni; Pietrosemoli, P; Pecorari, M; Leonardi, G; Torelli, Giuseppe; Luppi, Mario
abstract
n.d.
2007
- Fatal hemophagocytic syndrome related to active human herpesvirus-8/Kaposi sarcoma-associated herpesvirus infection in human immunodeficiency virus-negative, non-transplant patients without related malignancies
[Articolo su rivista]
Re, A; Facchetti, F; Borlenghi, E; Cattaneo, C; Capucci, Ma; Ungari, M; Barozzi, Patrizia; Vallerini, Daniela; Potenza, Leonardo; Torelli, Giuseppe; Rossi, G; Luppi, Mario
abstract
Hemophagocytic syndrome (HS) may occur as a consequence of herpes viral infections. Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus has so far been recognized as a trigger of HS only in immunosuppressed subjects or in patients with Kaposi sarcoma and/or HHV-8-related lymphoproliferative diseases. We report two Italian human immunodeficiency virus (HIV)-negative elderly men who developed an HS with a rapidly fatal course, following treatment with corticosteroids for autoimmune hemolytic anemia. An overwhelming active infection with HHV-8 was unequivocally documented by molecular and immunohistochemical methods, in the absence of HHV-8-related tumors. The occurrence of HHV-8-associated HS, although rare, may be considered, even out of the HIV or the transplantation settings, at least in areas endemic for HHV-8 infection.
2007
- Helicobacter pylori infection andchronic immune thrombocytopenic purpura: long-term results of bacteriumeradication and association with bacterium virulence profiles
[Articolo su rivista]
Emilia, Giovanni; Luppi, Mario; Zucchini, Patrizia; Morselli, M; Potenza, Leonardo; Forghieri, Fabio; Volzone, F; Jovic, Gordana; Leonardi, G; Donelli, A; Torelli, Giuseppe
abstract
Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.
2007
- May the correlation between Kit-D816 mutation and AML1-ETO level change the use of prognostic factors in t(8;21) AML?
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Riva, Giovanni; Zucchini, Patrizia; Morselli, M; Volzone, F; Forghieri, Fabio; Torelli, Giuseppe; Ottaviani, E; Martinelli, G.
abstract
n.d.
2007
- SVILUPPO DI IPOGAMMAGLOBULINEMIA IN PAZIENTI TRATTATI CON IMATINIB PER LEUCEMIA MIELOIDE CRONICA O TUMORI STROMALI GASTROINTESTINALI
[Abstract in Atti di Convegno]
Santachiara, R.; Leonardi, G.; Vallisa, D.; Maffei, R.; Martinelli, S.; Ferrari, A.; Alfieri, P.; Luppi, G.; Bertolini, F.; Piacentini, F.; Marasca, R.; Torelli, G.
abstract
NA
2006
- Diagnosis of occult tuberculosis in hematological malignancy by enumeration of antigen-specific T cells.
[Articolo su rivista]
Richeldi, Luca; Luppi, Mario; Losi, Monica; Luppi, Fabrizio; Potenza, Leonardo; Roversi, P; Cerri, Stefania; Millington, Ka; Ewer, K; Fabbri, Leonardo; Torelli, Giuseppe; Lalvani, A.
abstract
n.d.
2006
- Gene expression profiling of acute promyelocytic leukaemia identifies two subtypes mainly associated with Flt3 mutational status
[Articolo su rivista]
Marasca, Roberto; Maffei, Rossana; Zucchini, Patrizia; Castelli, Ilaria; Saviola, A; Martinelli, Silvia; Ferrari, Alberto; Fontana, M; Ravanetti, S; Torelli, Giuseppe
abstract
Acute promyelocytic leukaemia (APL) is a well-defined disease characterized by a typical morphology of leukaemic cells, the presence of t(15;17) translocation and the unique sensitivity to the differentiating effect of all-trans retinoic acid. Nevertheless, some aspects are variable among APL patients, with differences substantially related to morphological variants, peripheral leukocytes count, the presence of a disseminated intravascular coagulopathy, different PML/RAR alpha isoforms ( long, variable or short) and Fms-like tyrosine kinase 3 (Flt3) mutations. In order to better define this variability, we investigated the gene expression profiles of 18 APL cases revealing, besides a high uniformity in gene expression pattern, the presence of few robust differences among patients able to identify, by an unsupervised analysis, two major clusters of patients characterized by different phenotypes (hypogranular M3v vs classical M3) and by the presence or absence of Flt3 internal tandem duplications (ITDs). Further supervised analysis confirmed that Flt3 status was the APL parameter best associated with these two subgroups. We identified, between Flt3 wild-type and Flt3-ITDs subsets, 147 differentially expressed genes that were involved in the cytoskeleton organization, in the cell adhesion and migration, in the proliferation and the coagulation/inflammation pathways as well as in differentiation and myeloid granules constitution suggesting a role of Flt3 mutations in the pathogenesis and clinical manifestations of APL.
2006
- Human herpesvirus 6 latency characterized by high viral load: Chromosomal integration in many, but not all, cells
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Bosco, Raffaella; Vallerini, Daniela; Potenza, Leonardo; Forghieri, Fabio; Torelli, Giuseppe
abstract
n.d.
2006
- Isolated extramedullary relapse after autologous bone marrow transplantation for acute myeloid leukemia: Case report and review of the literature
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Riva, Giovanni; M., Morselli; Ferrari, Alberto; Imovilli, Annalisa; F., Giacobbi; Temperani, Paola; A., Donelli; Narni, Franco; Torelli, Giuseppe
abstract
Isolated extramedullary relapse (IEMR) is a pattern of acute myeloid leukemia (AML) relapse post-allogeneic bone marrow transplantation (alloBMT). Less is known about IEMR post-autologous BMT (autoBMT) and about factors associated with IEMR. We report a case of a woman with M4 AML who experienced IEMR post-autoBMT and review the related literature. Seventy-two alloBMT and 3 autoBMT patients, including ours, were identified. The review suggests that an M2 or M4 French-American-British (FAB) phenotype, intermediate cytogenetic risk group, and chromosome 8 abnormalities are more frequently associated with the occurrence of IEMR. IEMR occurs earlier in autoBMT than in alloBMT. Combined treatment with radiation and high-dose chemotherapy may be effective. When we searched the European Bone Marrow Transplant Registry (EBMTR) database, we found the incidence of IEMR to be statistically greater in alloBMT than in autoBMT (11% vs. 6%; P = 0.02), but no correlations have been found with the conditioning transplant regimen used. A closer follow-up, including body and central nervous system scan, should be considered in patients who are undergoing BMT presenting with several IEMR-associated factors.
2006
- KSHV/HHV-8 infection of tubular epithelial cells in transplantation kidney
[Articolo su rivista]
Barozzi, Patrizia; R., Bosco; Vallerini, Daniela; Potenza, Leonardo; Torelli, Giuseppe; Luppi, Mario; F., Facchetti; Guaraldi, Giovanni; T. F., Schulz
abstract
n.d.
2006
- More on: Platelet count and the Use of Recombinant Factor VIIa for the treatment of Bleeding Complications after Hematopoietic Stem Cell Transplantation
[Articolo su rivista]
Marietta, M; Facchini, L; Girardis, Massimo; Luppi, Mario; Torelli, Giuseppe
abstract
n.d.
2006
- Ocular involvement as first sign of isolated CNS relapse in diffuse large B-cell lymphoma
[Articolo su rivista]
A., Ferrari; Luppi, Mario; A., Lazzerini; Potenza, Leonardo; Cavallini, Gian Maria; Torelli, Giuseppe
abstract
A 52-year-old man was diagnosed with stage IVB non-Hodgkin lymphoma of diffuse large B-cell lymphoma subtype that involved the bone marrow and liver. Analysis of serum samples showed a raised concentration of lactate dehydrogenase, suggesting a high–intermediate risk of non-Hodgkin lymphoma according to the international prognostic index, but no HIV-1. The patient received six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab, and achieved complete remission. 6 months after diagnosis and 2 months after complete remission was achieved, the patient was admitted to hospital because of loss of vision. In the early phase of the examination, a fluorescein angiogram of the right eye (figure A) showed two large hyperfluorescent infiltrates with granularity (arrows) with small regions of retinal pigment epithelial detachments (arrowheads). In the late phase of the study, the left eye (figure B) showed a diffuse retinal pigment epithelial detachment that remained densely hypofluorescent (arrows), suggesting presence of lymphoma. However, bone-marrow biopsy and a CT scan of the neck, chest, and abdomen showed no relapse of lymphoma. 6 days later, the patient became somnolent and agitated, and developed confusion and lethargy. A CT scan (not shown) and an MRI of the brain (figure C) showed multifocal intraparenchymal lesions. Histological and immunohistochemical analysis of a stereotactic biopsy sample of one of the frontal lesions showed presence of B-lymphocyte antigen CD20-positive diffuse large B-cell lymphoma, and no presence of Epstein-Barr virus. The patient was given high-dose methotrexate followed by whole-brain radiotherapy. The patient died 1 month after CNS relapse because of disease progression.
2005
- Cytomegalovirus and ClostridiumDifficile co-infection in severe ulcero-hemorrhagic colitis during inductionchemotherapy for acute lymphoblastic leukemia
[Articolo su rivista]
Riva, Giovanni; Luppi, Mario; Potenza, Leonardo; Morselli, M; Ferrari, A; Saviola, Alessia; Volzone, F; Imovilli, Annalisa; Merighi, A; Maiorana, Antonino; Torelli, Giuseppe
abstract
Here we describe the first case of a biopsyprovenCytomegalovirus ulcero-hemorrhagic colitis,associated with Clostridium Difficile co-infection,occurring during standard induction chemotherapyfor common B cell acute lymphoblastic leukemia.We discuss the case and focalize clinical managementand diagnostic issues arising from it.
2005
- Efficacy of imatinib mesylate as maintenance therapy in adults with acute lymphoblastic leukemia in first complete remission
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Riva, Giovanni; Marasca, Roberto; Martinelli, Silvia; Torelli, Giuseppe
abstract
Seven Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients in first complete remission received maintenance therapy with imatinib alone. Two-year progression-free survival was 75%. Quantitative polymerase-chain-reaction (qPCR) monitoring of BCR-ABL showed that: (i) persisting molecular complete response (CR) was associated with long-lasting CR; (ii) molecular relapse did not invariably mean hematologic relapse; (iii) only the wide and rapid increment of BCR-ABL values was predictive of leukemia relapse.
2005
- Herpes simplex virus pneumonia during standard induction chemotherapy for acute leukemia: case report and review of literature.
[Articolo su rivista]
Ferrari, A.; Luppi, Mario; Potenza, Leonardo; Riva, Giovanni; Morselli, M.; Imovilli, A.; Volzone, F.; Rossi, G.; Codeluppi, M.; Guaraldi, Giovanni; Torelli, Giuseppe
abstract
Reactivation of latent HSV is the most common viral infection in patients during the profound neutropenia that occurs during remission induction in patients with lymphoma and acute leukemia and during the conditioning phase of bone marrow transplantation. We report here the occurrence of HSV-1 pneumonia in a patient with B-cell common ALL.
2005
- Human Cytomegalovirus, Human Herpesvirus 8 and Other Herpesviruses (Part III, Section 2, Chapter 75)
[Capitolo/Saggio]
Maciejewski, J. P.; Luppi, Mario; Torelli, Giuseppe
abstract
Written by a young, innovative author group, this exciting new book gives you the clinically relevant aspects of hematology in an innovative, unique format. The book is structured to comprehensively cover the complete scope of hematology, but allows fast access to key information you need in everyday practice. A section on consultative hematology includes chapters on special populations (pregnancy, pediatrics, geriatrics), infections of marrow and blood, and hematologic problems of medical practice and surgery. You'll also find a section on tools for the hematologist, covering clinical aspects of transfusion, transplantation, and the latest innovative laboratory procedures.
2005
- Immunoglobulin mutational status detected through single-round amplification of partial VH region, represents a good prognostic marker for the clinical outcome in chronic lymphocytic leukemia
[Articolo su rivista]
Marasca, Roberto; Maffei, Rossana; M., Morselli; Zucchini, Patrizia; Castelli, Ilaria; Martinelli, Silvia; M., Fontana; S., Ravanetti; M., Curotti; G., Leonardi; K., Cagossi; G., Partesotti; Torelli, Giuseppe
abstract
The immunoglobulin (Ig) mutational status in B-cell chronic lymphocytic leukemia (CLL) distinguishes two subsets of patients with different prognosis. Ig status detection is commonly performed with a panel of VH family-specific primers. Although this method detects clonal VDJ rearrangement in virtually all cases, it is technically cumbersome and therefore not widely used clinically. Here, we describe a simple and rapid method to establish the mutational status of IgVH in CLL. The method is based on a consensus VH FR2 primer, used in both polymerase chain reaction (PCR) and sequencing reactions. Overall, monoclonal B-cell populations were detected in 163 of 189 CLL patients (86%). The prognostic value of IgVH mutational status was then evaluated by analyzing survival in 146 CLL cases using different VH homology cutoffs. CLL prognostic groups were best separated by the classical 98% cutoff: median survival was 127 and 206 months in unmutated and mutated CLL cases, respectively (P = 0.0023). VH FR2 consensus and VH family PCR were compared in 41 cases, correctly assigning all cases by both methods. Therefore, we suggest a sequential strategy to detect immunoglobulin mutational status in CLL patients by first using the approach described in this study followed by alternative VH family-specific PCRs for negative cases.
2005
- Infectious agents and human immune diseases: Lessons from Helicobacter pylori
[Articolo su rivista]
Emilia, G; Luppi, Mario; Torelli, Giuseppe
abstract
n.d.
2005
- Pneumonia in acute leukaemia:blossoming culprits
[Articolo su rivista]
Potenza, Leonardo; Riva, Giovanni; Luppi, Mario; Torelli, Giuseppe
abstract
n.d.
2005
- Suppressive effect of human herpesvirus-8/Kaposi sarcoma-associated herpesvirus on in vitro colony formation of hematopoietic progenitor cells
[Articolo su rivista]
Luppi, Mario; Trovato, R; Barozzi, Patrizia; Gibellini, F; Potenza, Leonardo; Riva, Giovanni; Torelli, Giuseppe
abstract
n.d.
2005
- Transition of polycythemia vera to chronic myeloid leukaemia
[Articolo su rivista]
A., Saviola; C., Fiorani; L., Ferrara; V., Mazzocchi; P., Zucchini; Temperani, Paola; G., Longo; G., Emilia; Torelli, Giuseppe
abstract
A 77-year-old female with polycythemia vera (PV) showed a sudden, typical chronic myeloid leukaemia (CML), 8 yr after the initial diagnosis, and an intermittent treatment with hydroxyurea (0.5-1 g/d) and phlebotomies. At PV diagnosis, the Ph chromosome was negative and no bcr-abl rearrangement was observed; they were both revealed positive at CML onset. Transition of PV to CML is very rare; only seven substantiated cases had been reported in the literature up until now (six from 1964 to 1993). All patients but one received P-32 or alkylating agents for PV treatment. The pathogenetic mechanisms are briefly discussed.
2005
- Treatment of herpesvirus associated primary effusion lymphoma with intracavity cidofovir
[Articolo su rivista]
Luppi, Mario; Trovato, R; Barozzi, Patrizia; Vallisa, D; Rossi, Giorgio; Re, A; Ravazzini, L; Potenza, Leonardo; Riva, Giovanni; Morselli, M; Longo, G; Cavanna, L; Roncaglia, R; Torelli, Giuseppe
abstract
n.d.
2004
- A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia
[Articolo su rivista]
Potenza, Leonardo; B., Sinigaglia; Luppi, Mario; M., Morselli; A., Saviola; A., Ferrari; Riva, Giovanni; Zucchini, Patrizia; F., Giacobbi; G., Emilia; Temperani, Paola; Torelli, Giuseppe
abstract
A t(11;20)(p15;q11) is a rare but recurrent chromosomal aberration, reported in one case of polycythemia vera and a few cases of de novo acute myelocytic leukemia (AML) and therapy-related myelodysplastic syndrome (t-MDS). In t-MDS cases, the translocation resulted in the NUP98/TOP1 fusion transcript. The NUP98 gene has been suggested as the target for therapy-related malignancies. The reciprocal TOP1/NUP98 chimera, however, has not yet been encountered. We report a further case of de novo AML, subtype M2 in the French-American-British (FAB) classification, in which the reverse-transcriptase polymerase chain reaction (RT-PCR) revealed the NUP98/TOP1 chimera and also, for the first time, its reciprocal TOP1/NUP98. The literature review disclosed that, among six cases of de novo AML with t(11;20), the NUP98 gene was shown to be involved in one case and the NUP98/TOP1 chimera was detected in another. The translocation seems to be frequently associated with the FAB M2 subtype, younger age, hyperleukocytosis, and poor prognosis; thus, this translocation may identify a subset of not-therapy-related AML patients with shared clinical features.
2004
- AUTOLOGOUS STEM CELL TRANSPLANTATION FOR NEWLY DIAGNOSED FOLLICULAR LYMPHOMAS: LOW TOXICITY AND EXTENDED PROGRESSION FREE SURVIVAL. R1235 Barcelona, Spain. Bone Marrow Transplantation March 2004, Volume 33, Supplement 1
[Abstract in Rivista]
Narni, Franco; A., Donelli; A., Cuoghi; P., Bresciani; Pozzi, Samantha; Marasca, Roberto; G., Leonardi; M., Morselli; Luppi, Mario; G., Longo; Torelli, Giuseppe
abstract
In spite of an indolent course, advanced stage follicularlymphomas (FL) are incurable with conventional chemotherapy.High dose therapy could be investigated in selected patients,provided toxicity were acceptable. Improvements in supporttherapy and the widespread use of peripheral blood stem cells(SC) have made autologous transplantation a relatively safeprocedure. This prompted us to start a pilot study and, since1995, 23 patients have been enrolled at our center. Median agewas 49 (26 - 65). Most patients (80%) had stage IV disease andbone marrow involvement. For patients who achieved a completeresponse or a good partial response after CHOP, SC weremobilized with cyclophosphamide or DHAP plus G-CSF, andhigh dose therapy consisted of BEAM. High risk patients or poorresponders (residual high tumor burden or bone marrowinfiltration >50%) switched to a program of high dose sequentialtherapy. Nine patients received not-manipulated hematopoieticSC, 7 received ''ex vivo'' purged SC (6 by CD34+ positiveselection; 1 by positive+negative selection), and 8 patientsunderwent ''in vivo'' purging with anti-CD20 monoclonal antibody(rituximab). Residual disease was monitored at different steps bynested PCR. Treatment was well tolerated, with a median time toengrafment of 9 days (7-12), and a median stay in hospital of 22days (15-35). RBC and platelet transfusions were necessary,respectively, in 52% and 100% of the patients. The meannumber of RBC and platelet units given to transfused patientswas, respectively, 2.2 (1-5) and 3.7 (1-7). Fever occurred in 52%of the patients (mean 2,8 days in febrile patients) and mucositisin 85%. We did not observe, so far, any case of myelodysplasiaor secondary cancer. With a median FU of 58 (8-95) monthsfrom transplant, all patients are alive, 5 have relapsed, and 5-years estimated PFS is 70%. CD34+ selection had no impact onrelapse. In one patient, molecular response could be restoredand maintained by rituximab alone. Only a few data have beenpublished regarding autologous transplantation in FL patients atdiagnosis. Although the FU is relatively short and the number ofpatients still small, the present data suggest that autologoustransplant is a safe and effective therapy for selected, not heavilypretreated young patients with advanced stage disease.Especially since ''in vivo'' purging strategies can easily be carriedout, autologous SC transplantation should be investigated inrandomized trials.
2004
- Autologous stem cell transplantation for newly diagnosed follicular lymphomas: low toxicity and extended progression free survival
[Articolo su rivista]
Narni, Franco; Donelli, A; Cuoghi, A; Bresciani, P; Pozzi, S; Marasca, Roberto; Leonardi, G; Morselli, M; Luppi, Mario; Longo, G; Torelli, Giuseppe
abstract
2004
- Cardiac involvement in malignancies. Case 2. Right ventricular lesion as presenting feature of acute promyelocytic leukemia
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Morselli, M; Riva, Giovanni; Saviola, A; Ferrari, Alberto; De Santis, M; Rossi, Rosario; Torelli, Giuseppe
abstract
N/A
2004
- Helicobacter pylori and idiopathic thrombocytopenic purpura
[Articolo su rivista]
Emilia, G; Luppi, Mario; Torelli, Giuseppe
abstract
n.d.
2004
- Is it now the time to update treatment protocols for lymphomas with new anti-virus systems?
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Potenza, Leonardo; Riva, Giovanni; Morselli, M; Torelli, Giuseppe
abstract
n.d.
2004
- Myocardial ischemia in a patient with acute lymphoblastic leukemia during L-asparaginase therapy
[Articolo su rivista]
Saviola, A; Luppi, Mario; Potenza, Leonardo; Morselli, M; Bresciani, P; Ferrari, Alberto; Riva, Giovanni; Torelli, Giuseppe
abstract
Haemostatic abnormalities may occur in 1-2% of patients treated with L-asparaginase. Here, we present the second case of a myocardial infarction, developing in a patient with acute lymphoblastic leukemia (ALL), in the course of L-asparaginase treatment. In our patient and in the only one reported case from the literature, a recent exposure to vincristine and daunorubicin was also reported, but induction chemotherapy program was completed as scheduled, with the only withdrawal of L-asparaginase. Myocardial infarction should be included in the list of thrombotic complications possibly associated with L-asparaginase treatment, or with a combination of L-asparaginase and vinca alkaloids/anthracycline.
2004
- Thrombotic complications associated with thalidomide in multiple myeloma: an old problem with new questions and quandaries in decision-making
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Morselli, M; Saviola, A; Ferrari, Alberto; Riva, Giovanni; Longo, G; Marietta, M; Torelli, Giuseppe
abstract
n.d.
2003
- A simple and safe nomogram for the management of oral anticoagulation prior to minor surgery
[Articolo su rivista]
Marietta, M.; Bertesi, M.; Simoni, L.; Pozzi, S.; Castelli, I.; Cappi, C.; Torelli, G.
abstract
In 80 consecutive, anticoagulated patients scheduled for minor surgery, we reduced warfarin daily dosage by 50% on days 4, 3 and 2 before the surgery, restoring the original dose the day immediately before surgery. The evening after surgery, patients took a double warfarin dose, and then the usual maintenance dose was reintroduced. The mean International Normalized Ratio (INR) value assessed 1 week before surgery was 2.63 (range 1.88-3.87); it decreased at the moment of performing surgery to 1.68 (range 1.42-2.20; P < 0.05 with respect to the preoperative value), and returned to 2.43 7 days after (range 1.96-3.51, P = ns with respect to the preoperative value). No significant difference was found comparing prothrombin fragment 1.2 (F1.2) levels 1 week before surgery and on the morning of surgery (0.49 ng/ml vs 0.67 ng/ml, P = ns), suggesting that no activation of blood coagulation had taken place following the reduction of anticoagulant therapy. Patients developed neither major nor minor bleeding, nor thromboembolism during the procedures or up to I month after surgery. In our experience, this method for the management of anticoagulation before minor surgery has been shown to be safe and useful, avoiding the cumbersome shift to either intravenous or subcutaneous heparin.
2003
- Acquired haemophilia in HIV negative, HHV-8 positive multicentric Castleman's disease: a case report
[Articolo su rivista]
M., Marietta; Pozzi, Samantha; Luppi, Mario; M., Bertesi; C., Cappi; M., Morselli; Torelli, Giuseppe
abstract
Multicentric Castleman's Disease (MCD) is an atypical lymphoproliferative disorder, related to human herpesvirus 8 (HHV-8) infection and often associated with autoimmune diseases such as haemolytic anaemia and thrombocytopenia. Acquired haemophilia (AH) is a rare, life-threatening disease, which can occur in association with lymphoproliferative disorders, although only one case of AH in MCD has been described so far. We report the case of a human immuno deficiency virus negative 71-yr-old woman referred to our hospital for prolonged bleeding on surgical site following a lymph node biopsy. Lymph node histology revealed MCD, while the screening for the bleeding disorder showed prolonged activated partial thromboplastin time (APTT) (ratio: 1.89, normal value <1.24), low factor VIII (FVIII:C) levels (6%) with anti-factor VIII antibodies (2.3 Bethesda units), leading to a diagnosis of AH. Virological studies on plasma, lymphocyte and bronchoalveolar wash showed positivity for HHV-8 infection. Treatment with steroids (metilprednisolone 1-1.5 mg/kg/d) and cyclophosphamide (100 mg/d orally) was unsuccessful, and then antiviral therapy with cidofovir (5 mg/kg/wk) was started. A transient normalisation of APTT was seen after two administrations of cidofovir, but then coagulation parameters worsened and a large haematoma of the arm appeared. Bleeding was successfully stopped with two boluses of recombinant activated factor VII (Novoseven 90 microg/kg). Therapy with anti-CD 20 monoclonal antibody rituximab (Mabthera 375 mg/m2 once a week for 4 wk) was started, and following two administrations APTT normalised once again. Cardiological and neurological complications arose before the third dose of rituximab and the patient died shortly afterwards.
2003
- Erratum: Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors (Nature Medicine (2003) 9 (554-561))
[Articolo su rivista]
Barozzi, P.; Luppi, M.; Facchetti, F.; Mecucci, C.; Alu, M.; Sarid, R.; Rasini, V.; Ravazzini, L.; Rossi, E.; Festa, S.; Crescenzi, B.; Wolf, D. G.; Schulz, T. F.; Torelli, G.
abstract
2003
- Human herpesvirus 8-associated diseases in solid-organ transplantation: importance of viral transmission from the donor
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Guaraldi, Giovanni; L., Ravazzini; Rasini, Valeria; C., Spano; Riva, Giovanni; Vallerini, Daniela; Ad, Pinna; Torelli, Giuseppe
abstract
No abstract available
2003
- Immune thrombocytopenic purpura and Helicobacter pylori infection
[Articolo su rivista]
M., Morselli; Potenza, Leonardo; Luppi, Mario; Torelli, Giuseppe; G., Emilia
abstract
No abstract available
2003
- KSHV reactivation in post-transplant Kaposi sarcoma - Reply
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Facchetti, F; Schulz, Tf; Torelli, Giuseppe
abstract
No Abstract available
2003
- Late occurrence of hepatic veno-occlusive disease following gemtuzumab ozogamicin: successful treatment with defibrotide
[Articolo su rivista]
Saviola, A; Luppi, Mario; Potenza, Leonardo; Morselli, M; Ferrari, Alberto; Riva, Giovanni; Torelli, Giuseppe
abstract
No abstract available
2003
- Leukaemic pulmonary infiltrates in adult acute myeloid leukaemia: a high-resolution computerized tomography study
[Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Morselli, M; Tonelli, S; D'Apollo, N; Facchini, L; Torricelli, Pietro; Tazzioli, Giovanni; Saviola, A; Bresciani, P; Longo, G; Torelli, Giuseppe
abstract
Leukaemic infiltration of the lungs may occur in acute myeloid leukaemia (AML). Pulmonary infiltrates are usually microscopic and invariably associated with hyperleucocytosis. Four AML patients with respiratory symptoms and low leucocyte counts underwent standard chest radiography, bronchoscopy with bronchoalveolar lavage and high-resolution computerized tomography (HRCT) of the lungs. HRCT scans showed pulmonary infiltrates with alveolar, interstitial, mixed and peribronchial/perivascular patterns in all patients, including one with negative standard radiographic findings. Infectious agents were excluded. Histology of the lung biopsy/autopsy specimens showed leukaemic infiltrates. Pulmonary leukaemia may be the cause of pulmonary infiltrates, even in non-hyperleucocytosic AML patients with low blast counts.
2003
- Mysticism to medicine
[Articolo su rivista]
Barozzi, Patrizia; Luppi, Mario; Torelli, Giuseppe
abstract
No abstract available
2003
- Necrotising dermatitis in refractory acute myeloid leukaemia
[Articolo su rivista]
D'Apollo, N; Saviola, A; Longo, G; Luppi, Mario; Emilia, G; Torelli, Giuseppe
abstract
Severe cutaneous infections in leukaemic patients are difficult to treat and can rapidly become fatal. We report on a case of essential thrombocythemia evolved to a myelodysplastic syndrome and finally, to an overt myeloid leukaemia, refractory to chemotherapy. In the presence of a marked neutropenia, the patients developed a wide Staphylococcus epidermidis necrotising dermatitis. The diagnosis was made possible only by a skin biopsy culture and the antibiotic treatment, based on antimicrobial susceptibility tests, rapidly resolved the infection. In neutropenic patients, appropriate laboratory tests and treatment, can lead to recovery of life-threatening infections.
2003
- Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors
[Articolo su rivista]
Barozzi, Patrizia; Luppi, Mario; F., Facchetti; C., Mecucci; Alu, M.; R., Sarid; V., Rasini; L., Ravazzini; E., Rossi; S., Festa; B., Crescenzi; Dg, Wolf; Tf, Schulz; Torelli, Giuseppe
abstract
Kaposi sarcoma (KS) is a vascular tumor that can develop in recipients of solid tissue transplants as a result of either primary infection or reactivation of a gammaherpesvirus, the KS-associated herpesvirus, also known as human herpesvirus-8 (HHV-8). We studied whether HHV-8 and the elusive KS progenitor cells could be transmitted from the donor through the grafts. We used a variety of molecular, cytogenetic, immunohistochemical and immunofluorescence methods to show that the HHV-8-infected neoplastic cells in post-transplant KS from five of eight renal transplant patients harbored either genetic or antigenic markers of their matched donors. These data suggest the use of donor-derived HHV-8-specific T cells for the control of post-transplant KS.
2003
- Skin cancers after organ transplantation
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Torelli, Giuseppe
abstract
No abstract available
2002
- 'Gloves and socks' papular purpuric syndrome following primary infection with parvovirus B19: a link between dermatologists and haematologists
[Articolo su rivista]
Tonelli, S; Luppi, Mario; Morselli, M; Facchini, L; Potenza, Leonardo; Torelli, Giuseppe
abstract
No abstract available
2002
- HHV-8 infection in the transplantation setting: A concern only for solid organ transplant patients?
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Rasini, Valeria; Torelli, Giuseppe
abstract
Early epidemiologic studies have shown an increased risk of Kaposi sarcoma (KS) in recipients of solid organ transplants, while KS is exceptional in the setting of autologous and allogeneic bone marrow (BM) and peripheral blood stem cell (PBSC) transplant patients. The recent discovery of human herpesvirus 8 (HHV-8) as the necessary etiologic agent of KS has stimulated studies to assess whether KS is the result of HHV-8 transmission from the donor or of reactivation of a pre-existing HHV-8 infection in the recipient host. An association of HHV-8 infection with lymphoid neoplasias has also been observed, identifying this herpesvirus as a possible causal agent of some Epstein-Barr virus negative post-transplant lymphoproliferative diseases. The recent description of non-neoplastic complications associated with HHV-8 reactivation after autologous PBSC transplantation, has raised concerns about the spectrum of diseases potentially associated with this herpesvirus, even in the setting of BM and or PBSC transplantation. The issue of HHV-8 transmission with the grafts, the problems inherent with the diagnosis and monitoring of active viral infection, the need for prevention and treatment of the clinical consequences of HHV-8 primary infection and reactivation cannot be underestimated, at least in areas endemic for HHV-8 infection.
2002
- HOXA homeogene cluster interruption and dysregulation of HOAX9 in the blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia.
[Articolo su rivista]
Sinigaglia, B.; Giacobbi, F.; Zucchini, Patrizia; Maffei, Rossana; Marasca, Roberto; Torelli, Giuseppe; Temperani, Paola
abstract
HOXA homeogene cluster interruption and dysregulation of HOAX9 in the blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia
2002
- Helicobacter pylori infection and idiopathic thrombocytopenic purpura
[Articolo su rivista]
Emilia, G; Luppi, Mario; Morselli, M; Potenza, Leonardo; D'Apollo, N; Torelli, Giuseppe
abstract
No abstract available
2002
- Human herpesvirus 8-associated primary effusion lymphoma in human immunodeficiency virus-negative patients: a clinico-epidemiologic variant resembling classic Kaposi's sarcoma
[Articolo su rivista]
Ascoli, V; Lo Coco, F; Torelli, Giuseppe; Vallisa, D; Cavanna, L; Bergonzi, C; Luppi, Mario
abstract
No abstract available
2002
- Idiopathic thrombocytopenic purpura, helicobacter pylori infection, and HLA class II alleles [3] (multiple letters)
[Articolo su rivista]
Veneri, D.; Gottardi, M.; Guizzardi, E.; Zanuso, C.; Krampera, M.; Franchini, M.; Emilia, G.; Luppi, M.; Morselli, M.; Longo, G.; Torelli, G.
abstract
2002
- Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.
[Articolo su rivista]
Emilia, G; Morselli, M; Luppi, Mario; Longo, G; Marasca, Roberto; Gandini, G; Ferrara, L; D'Apollo, N; Potenza, Leonardo; Bertesi, M; Torelli, Giuseppe
abstract
Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies Is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITR CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical Improvement In 10 patients (83.3%). Five had a complete response (41.1%),4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even In patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITR
2002
- Low-molecular-weight heparin for vertebral artery dissection
[Articolo su rivista]
Marietta, M; Bertesi, M; Rozzi, N; Cano, Mc; Vallone, S; Cappi, C; Pozzi, S; Torelli, Giuseppe; Giuseppe,
abstract
A case of vertebral artery dissection and consequent basilar artery thrombosis in a 6-year-old patient is reported. The patient was treated with subcutaneous low-molecular-weight heparin at therapeutic doses (enoxaparin, 100 IU/kg twice daily) for 3 weeks, then reduced to 2,000 IU/day for 3 more weeks. After this time a magnetic resonance angiogram was obtained that showed complete recanalization of the left basilar artery. Enoxaparin proved to be a safe and useful therapy for thrombosis accompanying vertebral artery dissection.
2002
- Mixed warm and cold autoimmune hemolytic anemia: complete recovery after 2 courses of rituximab treatment
[Articolo su rivista]
M., Morselli; Luppi, Mario; Potenza, Leonardo; L., Facchini; S., Tonelli; D., Dini; G., Leonardi; A., Donelli; Narni, Franco; Torelli, Giuseppe
abstract
No abstract available
2002
- Response: Idiopathic thrombocytopenic purpura, Helicobacter pylori infection, and the HLA system
[Articolo su rivista]
Emilia, G; Luppi, Mario; Morselli, M; Longo, G; Torelli, Giuseppe
abstract
No abstract available
2002
- Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Rasini, V; Riva, Giovanni; Re, A; Rossi, Giorgio; Setti, G; Sandrini, S; Facchetti, F; Torelli, Giuseppe
abstract
We report the occurrence of human herpesvirus (HHV)-8 primary infection in an adult male kidney recipient. Four months after transplantation, the patient developed visceral Kaposi sarcoma, and 1 month later he presented with progressive and severe peripheral cytopenia, in the presence of a normocellular or hypercellular bone marrow (BM) with hemophagocytosis. HHV-8 was the sole pathogen detected by polymerase chain reaction either in the serum or in the BM. HHV-8 latent nuclear antigen was detected in immature progenitor cells from the BM. Immunosuppressive therapy was reduced, and the patient was treated with foscarnet for 2 weeks, leading to a dramatic normalization of blood cell counts, concomitantly with the disappearance of HHV-8 viremia. At the end of antiviral therapy, the patient received chemotherapy, and Kaposi sarcoma regressed in 2 months. Severe peripheral cytopenia may be a post-transplant complication after HHV-8 infection, for which treatment with foscarnet seems appropriate.
2002
- The role of molecular monitoring in autotransplantation for non-Hodgkin's lymphoma
[Articolo su rivista]
S., Galimberti; Marasca, Roberto; F., Caracciolo; R., Fazzi; F., Papineschi; E., Benedetti; F., Guerrini; F., Morabito; E., Oliva; N., Di Renzo; Federico, Massimo; M., Petrini; Torelli, Giuseppe
abstract
Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at diagnosis and after PBSCT, and on harvests in order to find a possible predictive role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out of 69 available bone marrows showed molecular involvement. Fifty-six percent of leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31 PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when transplanted with unpurged stem cells, whereas indolent NHL survival was not influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow; both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50% molecular remissions; the relapse rate was 55% for patients still PCR positive vs 29% for those who were PCR negative. Thus, after high-dose chemotherapy, close molecular monitoring of MRD using qualitative PCR techniques seems to represent a reliable prognostic indicator.
2001
- BCR-ABL rearrangement is not detectable in essential thrombocythemia.
[Articolo su rivista]
Emilia, G.; Marasca, Roberto; Zucchini, Patrizia; Temperani, Paola; Luppi, Mario; Torelli, Giuseppe; Lanza, F.; DE ANGELIS, C.; Gandini, D.; Castoldi, G.; Vallisa, D.; Cavanna, L.; del Senno, L.
abstract
BCR-ABL rearrangement is not detectable in essential thrombocythemia
2001
- Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura
[Articolo su rivista]
Emilia, G; Longo, G; Luppi, Mario; Gandini, G; Morselli, M; Ferrar, L; Amarri, S; Cagossi, K; Torelli, Giuseppe
abstract
Recent reports have suggested an association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP). The prevalence of H pylori infection and the effect of its eradication in a series of 30 ITP patients were investigated. H pylori infection has been documented in 13 patients (43.33%) by C-13 urea breath test and confirmed by histologic examination. Bacterium eradication with antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a complete response in 4 (33.33%) and to a partial response (platelets 90 x 10(9)/L120 x 10(9)/L) in 2 (16.66%). The response was maintained for a median of 8.33 months, but 1 patient relapsed 7 months after eradication. Search for H pylori infection seems appropriate in ITP patients at diagnosis. Bacterium eradication provides a new good option for a nonimmunosuppressive treatment in some ITP patients.
2001
- Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma
[Articolo su rivista]
Marasca, Roberto; Vaccari, Paola; Luppi, Mario; Zucchini, Patrizia; Castelli, Ilaria; Barozzi, Patrizia; A., Cuoghi; Torelli, Giuseppe
abstract
Nodal marginal zone B-cell lymphoma (NMZL) is actually considered as a distinct entity that must be distinguished from extra-nodal and splenic marginal zone Lymphomas. To define the cell origin and the role of antigen stimulation we determined the nucleotide sequence of the tumor-related immunoglobulin heavy chain variable genes in 10 cases of NMZL. The results were also evaluated on the basis of the presence of chronic hepatitis C virus (HCV) infection. All 10 cases harbored VH somatic mutations with a sequence homology compared to the closest germline gene, ranging from 83.33 to 98.28%. Interestingly, different VH segments were preferentially used in HCV-positive and HCV-negative patients: three of five HCV-negative NMZLs used a VH4-34 segment joined with different D and JH segments whereas three of five HCV-positive NMZLs used a VH1-69 gene joined with a D3-22 and a JH4 segment, with very strong similarities in the CDR3s among the three different cases. These data indicate: 1) NMZL is derived from B cells that have experienced the germinal center reaction; 2) the preferential usage of a VH1-69 segment in the majority of the HCV-positive NMZL cases with similar CDR3s suggests the presence of a common antigen, probably a HCV antigen epitope, involved in the B-cell selection; and 3) the use of a VH4-34 segment suggests a role of yet unknown B-cell superantigen(s) in the selection of tumor B-cell precursors in HCV-negative NMZL.
2001
- Unusual sites of malignancy: case 1. Primary non-Hodgkin's lymphoma of the hand in a patient with hepatitis C infection.
[Articolo su rivista]
Longo, G; Potenza, Leonardo; D'Apollo, N; Ferrara, L; Gandini, G; Bertesi, M; Torelli, Giuseppe; Emilia, G.
abstract
n.a.
2000
- Detection of antibodies to human herpesvirus 8 in Italian children: evidence for horizontal transmission
[Articolo su rivista]
D., Whitby; Luppi, Mario; C., Sabin; Barozzi, Patrizia; AR Di, Biase; Balli, Fiorella; F., Cucci; Ra, Weiss; C., Boshoff; Torelli, Giuseppe
abstract
Human herpesvirus 8 (HHV-8), also known as Kaposi´s sarcoma associated herpesvirus (KSHV), has been shown to be the causative agent for Kaposi´s sarcoma (KS) and to be more prevalent in populations or risk groups at increased risk for KS. HHV-8 infection is rare in children from the US and the UK, but has been reported in African children. In this study we examine HHV-8 infection in children from Italy, a country with an elevated prevalence of HHV-8 in adults and high socio-economic conditions.
2000
- Detection of circulating tumor by reverse transcriptase polymerase chain reaction [1] (multiple letters)
[Articolo su rivista]
Anderson, P. M.; Goeminne, J. -C.; Guillaume, T.; Federico, M.; Sabbatini, R.; Morselli, M.; Depenni, R.; Cagossi, K.; Luppi, M.; Torelli, G.; Silingardi, V.
abstract
2000
- Detection of circulating tumor cells by reverse transcriptase polymerase chain reaction of maspin in patients with breast cancer undergoing conventional-dose chemotherapy
[Articolo su rivista]
R., Sabbatini; Federico, Massimo; M., Morselli; Depenni, Roberta; K., Cagossi; Luppi, Mario; Torelli, Giuseppe; Silingardi, Vittorio
abstract
Purpose: To establish, in patients with breast cancer subjected to primary conventional chemotherapy and enrolled in a prospective study, the mobilizing effect of therapy on potentially neoplastic cells by means of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for mRNA of maspin, a protein related to the serpin family of protease inhibitors. Patients and Methods: Peripheral-blood samples were collected from 30 patients with histologically proven breast cancer before and 4 and 8 days after conventional chemotherapy for three consecutive courses. A total of 216 samples were screened for the presence of maspin mRNA by RT-PCR. Results: Before therapy, all samples but one were negative. After chemotherapy, 11 patients (38%) had positive samples. No difference in the rate of positivity was observed between groups defined according to initial stage, type of chemotherapy, Ki-67-related proliferative activity, or CA 15.3 expression. Conclusion: Our results confirm that RT-PCR for maspin mRNA is a sensitive assay for the study of circulating potentially neoplastic mammary cells in patients with breast cancer. Moreover, our findings indicate a marked effect of conventional-dose chemotherapy on the mobilization of these cells in breast tumors, In our series of patients, this phenomenon does not seem to be associated with other known risk factors. Finally, the data suggest, without proving, an association between the presence of circulating maspin positive cells and a higher risk of disease progression, If this association could be confirmed, then the assay could have prognostic significance. However, larger confir- matory studies are necessary.
2000
- Fatal herpesvirus-6 encephalitis in a recipient of a T-cell-depleted peripheral blood stem cell transplant from a 3-loci mismatched related donor
[Articolo su rivista]
Tiacci, E; Luppi, Mario; Barozzi, Patrizia; Gurdo, G; Tabilio, A; Ballanti, S; Torelli, Giuseppe; Aversa, F.
abstract
Human herpesvirus-6 (HHV-6), like all the other herpes viruses, remains latent in host cells after primary infection but can be reactivated In immuno-compromised patients causing fever, skin rash, bone marrow (BM) suppression, pneumonitis, Sinusitis and meningoencephalitis. We describe the case of a man with chronic myelogenous leukemia who developed encephalitis associated with acute graft-versus-host disease two months after a T-cell-depleted mismatched peripheral blood stem cell transplant. Magnetic resonance images of the brain revealed multiple bilateral foci of signal abnormality. HHV-6 was the only pathogen detected in cerebrospinal fluid by PCR. treatment with both ganciclovir and foscarnet was unsuccessful and the patient gradually deteriorated and died. Other cases of HHV-6 encephalitis after bone marrow transplantation are reviewed.
2000
- Gestational thrombocytopenia - Reply
[Articolo su rivista]
Emilia, Giovanni; Luppi, Mario; Marasca, Roberto; Torelli, Giuseppe
abstract
Although patients with essential thrombocythaemia (ET) do not have the Philadelphia chromosome t(9;22), which defines chronic myelocytic leukaemia, the chimeric BCR-ABL transcript mRNA from this translocation has been identified in patients with clinically typical essential thrombocythaemia”.These findings have been detected, by D Blickstein and colleagues2 in 48% of 25 patients negative for the Philadelphia chromosome who had essential thrombocythaemia, investigated by two-step nested RT-PCR. Some workers have not, however, been able to confirm these data by the same technique, in 18 and 20 such patients, respectively. [3] and [4] Moreover, others have shown the absence of the chimeric transcript in 41 patients with essential thrombocythaemia studied by the fluoresence in-situ hybridisation with a BCR-ABL probe.5We investigated 112 patients who had essential thrombocythaemia with long follow-up, by RT-PCR, and detected the BCR-ABL transcript in only one patient who progressed to myeloid blastic crisis 12 years after diagnosis. Actually, whether essential-thrombocythaemia patients negative for the Philadelphia chromosome express the BCR-ABL transcript has been a matter of controversy for several years. In studies, the apparent essential thrombocythaemia carrying the Philadelphia anomaly, cytogenetically or molecularly should probably be considered as a variant of chronic myelocytic leukaemia with thrombocytosis and often long survival, with obvious clinical and therapeutical implications.
2000
- Late-appearing PML/RAR alpha fusion transcript with coincidental t(12;13)(p13.2;q14) in acute promyelocytic leukemia lacking the t(15;17) cytogenetic anomaly
[Articolo su rivista]
Temperani, Paola; Luppi, Mario; F., Giacobbi; V., Medici; M., Morselli; Barozzi, Patrizia; Marasca, Roberto; Torelli, Giuseppe; Emilia, Giovanni
abstract
The late appearance of a cytogenetic/molecular hallmark in human leukemias is a rare event. We report on a case of acute myeloid leukemia with morphology, immunophenotype and clinical features typical of promyelocytic subtype (APL), in which the specific PML/RAR alpha gene rearrangement was molecularly detected only at second relapse of disease, without cytogenetic evidence of the t(15;17). The emergence of the PML/RAR alpha gene may be therapy-related or may represent the exceptional result of a clonal evolution during progression of neoplasia. At second relapse, a novel cell clone bearing a t(12;13)(p13.2;q14) was also observed and a molecular deletion and rearrangement of a locus at 13q14, distinct from retinoblastoma (Rb1) locus, was found. In this unusual case, the PML/RAR alpha product seems to be not essential for the expression of the promyelocytic phenotype at diagnosis and, when detectable, it is not the sole genetic defect. (C) 2000 Elsevier Science Inc. All rights reserved.
2000
- Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; G., Santagostino; R., Trovato; Tf, Schulz; Marasca, Roberto; D., Bottalico; L., Bignardi; Torelli, Giuseppe
abstract
In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of the orf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, single orf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.
2000
- Nonmalignant disease associated with human herpesvirus 8 reactivation in patients who have undergone autologous peripheral blood stem cell transplantation
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Tf, Schulz; R., Trovato; A., Donelli; Narni, Franco; J., Sheldon; Marasca, Roberto; Torelli, Giuseppe
abstract
Fever, cutaneous rash, and hepatitis-for which an infectious cause was suspected-developed in an Italian patient with non-Hodgkin lymphoma after autologous peripheral blood stem cell (PBSC) transplantation. Polymerase chain reaction (PCR) with degenerate primers for the highly conserved DNA polymerase gene of herpesviruses detected herpesvirus sequences 100% identical to human herpesvirus-8 (HHV-8) in serial cell-free serum samples, collected immediately before or concomitant with the occurrence of clinical symptoms; no other common infections were documented. The presence of the HHV-8 genome (clade C) was confirmed by PCR with HHV-8-specific primers for orf 26 and orf-K1, HHV-8 viremia was undetectable either before transplantation or when the patient was clinically asymptomatic. Semiquantitative PCR analysis showed variations of the viral load correlating with the clinical status. Anti-HHV-8 antibodies were detected before and after transplantation by an immunofluorescence assay for lytic antigens. Active HHV-8 infection may be associated with nonmalignant illness after PBSC/bone marrow transplantation. (Blood. 2000;96:2355-2357)
2000
- PCR with degenerate primers for highly conserved DNA polymerase gene of the herpesvirus family shows neither human herpesvirus 8 nor a related variant in bone marrow stromal cells from multiple myeloma patinets.
[Articolo su rivista]
Dominici, Massimo; Luppi, Mario; D., Campioni; F., Lanza; Barozzi, Patrizia; R., Milani; S., Moretti; G., Nadali; R., Spanedda; R., Trovato; Torelli, Giuseppe; G., Castoldi
abstract
The possibility has been raised that either a human herpesvirus-8 (HHV-8) variant or a novel, unidentified, gamma-herpesvirus related to HHV-8 is frequently associated with multiple myeloma (MM), which could explain the lack of antibodies to HHV-8 antigens and the discordant results from polymerase chain reaction (PCR) studies of HHV-8-specific sequences in MM patients. Thus, we used a sensitive PCR assay with degenerate primers targeting the highly conserved DNA polymerase gene of the herpesvirus family to examine the long-term cultures of bone marrow stromal cells (BMSCs) from 19 MM, 3 monoclonal gammopathies of undetermined significance and 6 control patients. Both the culture supernatant and the adherent stromal layer were examined from the 2nd until the 8th week of culture to assess the immunophenotype of the various cell types harvested for the molecular analysis. BMSCs consisted of a mixed population of fibroblast, macrophage, dendritic and endothelial cells. An amplified product of the expected size was obtained only in 3 MM cases, both in the adherent and nonadherent fractions. Direct sequencing and alignment of the nucleotide and amino acid sequences showed that the DNA sequences were 100% identical to Epstein-Barr virus (EBV) DNA. The PCR positivity was due to the presence of EBV-infected lymphoblastoid cells with plasmacytoid features, expressing the EBV-encoded latent membrane protein-1 and detectable either in the stromal cells or in the culture supernatant. Our data do not support a causal role of either HHV-8 or a novel herpesviral variant related to HHV-8 in MM.
2000
- REGIMEN-RELATED LIVER TOXICITY IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
[Abstract in Rivista]
Narni, Franco; A., Donelli; R., Sabbatini; A., Cuoghi; Silingardi, Vittorio; Torelli, Giuseppe
abstract
The incidence of hepatic veno-occlusive disease (VOD) varies in different series (1-65%), depending on the type of transplant and on the patients’ characteristics. Even in the setting of autologous HSTC, however, the frequency of this life threatening regimen-related toxicity is undetermined. We retrospectively analyzed the data of 165 consecutive patients transplanted between June 1995 and October 1999 at our Center. HBsAg and HCVAb positive patients were excluded. Diagnosis was: non-Hodgkin’s lymphoma (62), Hodgkin’s disease (11), multiple myeloma (20), leukemia (16), breast cancer (47), and others (9). Nineteen patients (7 MM, 8 BC, 3 OC, 1 HD) received double transplants. The source of hematopoietic stem cells was: BM (2%), PBPCs (86%), BM+PBPCs (6%), selected CD34+ cells (6%). The regimen was: BEAM (32%), Busulfan based regimens (11%), HD/L-PAM (13%), MTZ/L-PAM (9%), MTZ/TT/CY (13%), TT/L-PAM (17%), and other regimens (5%). The parameters we considered were: 1) bilirubin levels in the 4 weeks after transplant, 2) painful hepatomegaly, 3) ascites and/or unexplained weight gain. Other indices of liver damage (AST, ALT, -GT, etc.) were also considered. An increased bilirubin level above the base line was observed in most patients, with a median peak value of 0.8 mg/DL (mean 0.8, range 0.3-1.9). A transient increase in body weight (median increase 1.5%, mean 1.95%, range 0.5%-6.0%), that was promptly corrected by diuretics, was also observed in 60% of our patients. Nevertheless, no one of our patients met the commonly accepted criteria (Seattle and Baltimore criteria) for a clinical diagnosis of hepatic VOD. In only one patient with (MM) severe liver toxicity occurred 9 months after the second transplant, and multi-organ failure eventually developed. The conditioning regimen at the second transplant had been busulphan + L-PAM. This patient could have met the criteria for a clinical diagnosis of VOD, except for the late onset of the symptoms. Others have reported a higher incidence of hepatic VOD. This might be explained by the selection criteria of the patients in different series. In summary, in selected patients undergoing auto-HSC transplantation in the context of a front line treatment and receiving a variety of conditioning regimens, the frequency of hepatic VOD seems to be quite low.
1999
- Anticoagulant pseudothrombocytopenia with platelet satellitism
[Articolo su rivista]
Morselli, M; Longo, G; Bonacorsi, G; Potenza, Leonardo; Emilia, G; Torelli, Giuseppe
abstract
n.a.
1999
- Cellular localization of human herpesvirus 8 in nonneoplastic lymphadenopathies and chronic interstitial pneumonitis by in situ polymerase chain reaction studies
[Articolo su rivista]
Trovato, R; Luppi, Mario; Barozzi, Patrizia; Da Prato, L; Maiorana, Antonino; Lico, S; Marasca, Roberto; Torricelli, Pietro; Torelli, Giuseppe; Ceccherini Nelli, L.
abstract
Objectives: To study the cellular localization of human herpesvirus 8 (HHV-8) in rare cases of HHV-8 infection from Italy that are associated neither with human immunodeficiency virus (HIV) infection nor Kaposi's sarcoma (KS). Methods: The presence and distribution of HHV-8-infected cells was investigated by direct in situ polymerase chain reaction (PCR) in the lymph node tissues from 2 patients with reactive lymphadenopathies with florid follicular hyperplasia and increased vascularity and in the lung tissue from 1 patient with chronic interstitial pneumonitis. Results: HHV-8 was localized in lymphoid and monocyte-macrophage cells scattered in the interfollicular regions of both lymph nodes but not in endothelial cells. In the lung tissue, HHV-8 was found in the inflammatory cells infiltrating the interalveolar interstitium, in endothelial cells of the pulmonary vasculature, and in rare pneumocytes. Conclusions: HHV-8 can infect nonneoplastic lymph nodes of immunocompetent subjects, and the distribution of infected cells outside of the germinal centers resembles that of Epstein-Barr virus (EBV)-infected cells in the lymph nodes in the course of infectious mononucleosis. Endothelial cells and pneumocytes may be a target of HHV-8 infection out of the KS setting, at least in the presence of a chronic inflammatory process.
1999
- Erratum: Cellular localization of human herpesvirus 8 in nonneoplastic lymphadenopathies and chronic interstitial pneumonitis by in situ polymerase chain reaction studies (Journal of Human Virology (January/February 1999) 2:1 (38-44))
[Articolo su rivista]
Trovato, R.; Luppi, M.; Barozzi, P.; Da Prato, L.; Maiorana, A.; Lico, S.; Marasca, R.; Torricelli, P.; Torelli, G.; Ceccherini-Nelli, L.
abstract
1999
- Expression of cell-homologous genes of human herpesvirus-8 in human immunodeficiency virus-negative lymphoproliferative diseases
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Maiorana, Antonino; R., Trovato; Marasca, Roberto; M., Morselli; K., Cagossi; Torelli, Giuseppe
abstract
Human herpesvirus-8 (HHV-8) genome encodes for genes homologous to human cellular genes such as interleukin-6 (IL-6), Cyclin-D, BCL-5, and IL-8 receptor (G-protein-coupled receptor [GCR]), We used reverse transcriptase-polymerase chain reaction to study the expression of these viral genes in lymphoproliferative disorders associated with HHV-8 infection, None of these genes was expressed in 1 case of benign, localized Castleman´s disease (CD), and only viral IL-6 and viral Cyclin-D were transcribed in 2 cases of benign lymphadenopathies with giant germinal center hyperplasia and increased vascularity. In contrast, all 4 genes were transcribed in 1 case of multicentric CD of plasma cell type with aggressive clinical course and in 1 primary effusion lymphoma cell line. Our study provides the evidence that various HHV-8 genes, homologous to cellular genes involved in control of proliferation and apoptosis, may be differently expressed in different lymphoid disorders in vivo.
1999
- Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3
[Articolo su rivista]
Morris, C; Luppi, Mario; Mcdonald, M; Barozzi, Patrizia; Torelli, Giuseppe
abstract
An unusually high level of latent HHV-6 infection has been documented in the peripheral blood and/or bone marrow cells of a small group of patients with predominantly malignant lymphoid disorders, and in at least one healthy individual, We have shown previously in peripheral blood mononuclear cells (PBMCs) of three patients, two with a history of lymphoma and one with multiple sclerosis, a specific target site for latent integration of the full-length HHV-6 viral genome on the distal short arm of chromosome 17, in band p13.3. Fluorescence in situ hybridization (FISH) procedures were used to map more precisely the location of the viral integration site in one of those patients, relative to two known oncogenes mapped previously, namely CRK, and the more telomeric ABR oncogene. It is shown that the HHV-6 integration site is located at least 1,000 kb telomeric of ABR, and is very likely to map close to or within the telomeric sequences of 17p. This finding is significant given that human telomeric-like repeats flank the terminal ends of the HHV-6 genome. Cytogenetic studies showed evidence of karyotype instability in the peripheral blood cells infected latently. J. Med. Virol. 58:69-75, 1999.
1999
- Human herpesvirus 6 latently infects early bone marrow progenitors in vivo
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; C., Morris; Maiorana, Antonino; R., Garber; G., Bonacorsi; A., Donelli; Marasca, Roberto; A., Tabilio; Torelli, Giuseppe
abstract
We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways.
1999
- Human herpesvirus-8 infection in hemodialysis patients from northern Italy.
[Articolo su rivista]
Luppi, Mario; Vandelli, L.; Whitby, D.; Savazzi, A. M.; Barozzi, Patrizia; Medici, G.; Albertazzi, Alberto; Torelli, Giuseppe
abstract
No abstract available
1999
- Lack of confirmation of an association between HTLV-I infection and myelodysplastic syndrome
[Articolo su rivista]
M., Morselli; Luppi, Mario; Barozzi, Patrizia; Dominici, Massimo; Temperani, Paola; D., Campione; F., Lanza; R., Trovato; Marasca, Roberto; G., Longo; G., Emilia; Torelli, Giuseppe
abstract
No abstract available
1999
- Missense mutations in the PML/RAR alpha ligand binding domain in ATRA-resistant As2O3 sensitive relapsed acute promyelocytic leukemia
[Articolo su rivista]
Marasca, Roberto; Zucchini, Patrizia; S., Galimberti; G., Leonardi; Vaccari, Paola; A., Donelli; Luppi, Mario; M., Petrini; Torelli, Giuseppe
abstract
Background and Objectives. Acute promyelocytic leukemia is characterized by the chromosomal translocation t(15;17) which yields the fusion product PML/RAR alpha. Art-trans retinoic acid probably induces differentiation of atypical promyelocytes and clinical remission in APL patients by binding to the ligand binding domain (LBD) of the RAR alpha portion of the PML-RAR alpha chimeric protein. Structural alterations of the LED of the PML/RAR alpha have been revealed in ATRA-resistant APL cell lines and in a few APL patients with acquired clinical resistance to ATRA therapy. Two APL relapsed patients with clinical resistance to ATRA therapy were evaluated for the presence of nucleotide mutations in the LED of PML/RAR alpha gene and then treated with arsenic trioxide (As2O3). Design and Methods. DNA fragments from the LED of the PML/RAR alpha: chimeric transcript were obtained by reverse-transcribed polymerase chain reaction. Direct sequencing was performed by an unambiguous bidirectional automatic analysis. Samples representative of APL onset and relapse were analyzed from both patients. Results. In both patients, at the ATRA-resistant relapse, a missense point mutation in the LED of the PML/RAR alpha gene was found. The mutations, absent at APL onset, led to an Arg272Gln and to an Arg276Trp amino acid substitution, according to the sequence of the RAR alpha protein. Both patients had complete clinical and hematologic remission after treatment with As2O3. Interpretation and Conclusions. LED missense mutations appear to be a significant mechanism of acquired ATRA-resistance in vivo, closely related to clinical APL relapse. The two cases reported here provide the first in vivo evidence of Apt, relapsed patients, who have become ATRA-resistant for molecular reasons, being sensitive to arsenic trioxide.
1999
- Neither Human Herpesvirus 8 nor a related variant could be detected in bone marrow stromal cells from multiple myeloma patients.
[Abstract in Rivista]
Dominici, Massimo; Luppi, Mario; D., Campioni; F., Lanza; Barozzi, Patrizia; R., Milani; A., Latorraca; S., Moretti; Torelli, Giuseppe; G. L., Castoldi
abstract
The possibility has been raised that either a human herpesvirus-
8 (HHV-8) variant or a novel, unidentified, g-herpesvirus
related to HHV-8 is frequently associated with multiple
myeloma (MM), which could explain the lack of antibodies to
HHV-8 antigens and the discordant results from polymerase
chain reaction (PCR) studies of HHV-8-specific sequences in
MM patients. Thus, we used a sensitive PCR assay with degenerate
primers targeting the highly conserved DNA polymerase
gene of the herpesvirus family to examine the longterm
cultures of bone marrow stromal cells (BMSCs) from
19 MM, 3 monoclonal gammopathies of undetermined significance
and 6 control patients. Both the culture supernatant
and the adherent stromal layer were examined from the 2nd
until the 8th week of culture to assess the immunophenotype
of the various cell types harvested for the molecular analysis.
BMSCs consisted of a mixed population of fibroblast, macrophage,
dendritic and endothelial cells. An amplified product
of the expected size was obtained only in 3 MM cases, both in
the adherent and nonadherent fractions. Direct sequencing
and alignment of the nucleotide and amino acid sequences
showed that the DNA sequences were 100% identical to
Epstein-Barr virus (EBV) DNA. The PCR positivity was due
to the presence of EBV-infected lymphoblastoid cells with
plasmacytoid features, expressing the EBV-encoded latent
membrane protein-1 and detectable either in the stromal
cells or in the culture supernatant. Our data do not support
a causal role of either HHV-8 or a novel herpesviral variant
related to HHV-8 in MM.
1999
- PCR con primer degenerati non evidenzia sequenze virali di HHV-8 ne di una sua variante in cellule stromali midollari di pazienti affetti da gammopatie monoclonali
[Abstract in Rivista]
Dominici, Massimo; Luppi, Mario; D., Campioni; F., Lanza; Barozzi, Patrizia; R., Milani; S., Moretti; R., Spanedda; Torelli, Giuseppe; G. L., Castoldi
abstract
The association of human herpesvirus-8 (HHV-8) infection with multiple myeloma (MM) is still controversial. The possibility has been raised that either a HHV-8 variant or a novel, as yet unidentified, γ-herpesvirus related to HHV-8, are frequently associated with MM, which could explain the lack of antibodies to HHV-8 antigens and the discordant results from polymerase chain reaction studies (PCR) of HHV-8 specific genomic sequences in MM patients. Thus, we used a sensitive PCR assay with degenerate primers targeting the highly conserved DNA polymerase gene of the herpesvirus family to examine the long term-cultures (LTC) of bone marrow stromal cells (BMSCs) from 21 MM, 3 monoclonal gammopathy of undetermined significance (MGUS) and 6 control patients. Both the culture supernatant and the adherent stromal layer were examined from the 2nd until the 8th week of culture to assess the immunophenotype of the various cell types harvested for the molecular analysis. BMSCs consisted of a mixed population of fibroblast, macrophage, dendritic and endothelial cells. An amplified product of the expected size was obtained only in 3 MM cases, both in the adherent and non adherent fractions. Direct sequencing and alignment of the nucleotide and amino acidic sequences showed that the DNA sequences were 100% identical to Epstein-Barr virus DNA. PCR with specific primers targeting the latent membrane protein-1 (LMP-1) gene confirmed the presence of EBV. The PCR positivity was due to the presence of EBV infected lymphoblastoid cells (LCLs) with plasmacytoid features, expressing the LMP-1 protein and detectable either in the stromal cells or in the culture supernatant. Our data do not support a causal role of either HHV-8 or a novel herpesviral variant related to HHV-8 in MM, not even in the presence of EBV co-infection.
1999
- The oncogenic 30 and 69 bp deletion variants of the EBV LMP-1 gene are common in HIV-negative lymphoproliferations, both malignant and benign
[Articolo su rivista]
Barozzi, Patrizia; Luppi, Mario; K., Cagossi; Maiorana, Antonino; Marasca, Roberto; T., Artusi; S., Poggi; S. A., Pileri; Torelli, Giuseppe
abstract
BACKGROUND:
In vitro studies have shown that the 30 and 69 base pair (bp) deletion variants of the latent membrane protein (LMP)-1 gene of the Epstein-Barr virus (EBV) have a higher transforming capacity than the wild-type variant. In recent years these studies have triggered an in vivo search for such potentially oncogenic variants in lymphoid tissues.
PATIENTS AND METHODS:
We used polymerase chain reaction (PCR) to investigate the prevalence of LMP-1 gene variants in EBV-positive lymph nodes from 60 HIV-negative Italian patients with benign and malignant lymphoid disorders.
RESULTS:
The 30 bp variant was detected in 10 of 39 (25.6%) malignant lymphomas but also in 4 of 13 (30%) reactive lymphadenitis with follicular hyperplasia. Of note is the fact that the 69 bp variant was detected in three cases of malignant lymphoproliferation but also in two cases of localized Castleman's disease of hyalin vascular type.
CONCLUSIONS:
The molecular detection of the oncogenic variants of the LMP-1 gene in a lymph node biopsy as an indicator of the aggressiveness of the EBV-associated lymphoproliferative disease must be considered with caution. The relatively high frequency of the 69 bp variant in our series compared with that reported in the literature probably reflects a different incidence of LMP-1 variants in healthy populations from different geographical areas.
1998
- Absence of a directly causative role for human herpesvirus 7 in human lymphoma and a review of human herpesvirus 6 in human malignancy
[Articolo su rivista]
Berneman, Zn; Torelli, Giuseppe; Luppi, Mario; Jarrett, Rf
abstract
In search of a (new) viral etiological agent, we screened 64 lymph node samples from Hodgkin's disease (HD) and 43 samples (32 lymph node and 11 skin biopsies) from non-Hodgkin's lymphoma (NHL) for human herpesvirus 7 (HHV-7). Twenty-nine control samples were tested as well, including 17 with benign lymphadenopathy. None of the samples tested positive by Southern blot hybridization using HHV-7-specific probes, We conclude that there is no major HHV-7 load in human lymphoma and that HHV-7 is not likely to be directly involved in its etiology. This is in contrast to a small minority of human lymphoproliferative diseases in which HHV-6 can be found at high copy number, but in which an etiological role is still uncertain.
1998
- Age- and sex-specific seroprevalence of human herpesvirus 8 in Jamaica - Response
[Articolo su rivista]
Luppi, Mario; Whitby, D; Barozzi, Patrizia; Boshoff, C; Weiss, R; Cucci, F; Torelli, Giuseppe
abstract
No abstract available
1998
- Age- and sex-specific seroprevalence of human herpesvirus 8 in Jamaica [3] (multiple letters)
[Articolo su rivista]
Manns, A.; Strickler, H. D.; Hanchard, B.; Manassaram, D. M.; Waters, D.; Ablashi, D. V.; Luppi, M.; Whitby, D.; Barozzi, P.; Boshoff, C.; Weiss, R.; Cucci, F.; Torelli, G.
abstract
1998
- Alpha-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Group on ET
[Articolo su rivista]
Sacchi, Stefano; Gugliotta, L; Papineschi, F; Liberati, Am; Rupoli, S; Delfini, C; Ruggeri, M; Cavanna, L; Bucalossi, A; Benedetti, E; Ferrandina, C; Vinci, G; Morselli, M; Torelli, Giuseppe
abstract
The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.
1998
- Assessment of platelet function in pregnancy with the PFA-100 (TM) system
[Abstract in Atti di Convegno]
Marietta, M; Neri, Isabella; Piccinini, F; Facchinetti, Fabio; Bertesi, M; Torelli, Giuseppe
abstract
Assessment of platelet function in pregnancy with the PFA-100 (TM) system
1998
- Chronic myeloid leukemia with thrombocythemic onset may be associated with different BCR/ABL variant transcripts
[Articolo su rivista]
Emilia, Giovanni; Luppi, Mario; Ferrari, Mg; Temperani, Paola; Marasca, Roberto; Giacobbi, F; Vaccari, Paola; Bandieri, E; Di Donato, C; Carapezzi, C; Torelli, Giuseppe
abstract
Ph-positive chronic myeloid leukemia (CML) mimicking essential thrombocythemia (ET) at onset seems to be a distinct clinical entity. Whether this rare clinical form of CML is associated with single, specific variants of BCR/ABL transcripts is a matter of debate. Among 82 consecutive patients with Ph-positive CML, we identified 3 patients in which the disease mimicked ET at presentation, because-of marked thrombocytosis and moderate leukocytosis, with few immature myeloid cells in peripheral blood and blood basophilia in 2 of them. Molecular analysis with the reverse transcriptase-polymerase chain reaction technique showed the presence of b2a2, b3a2, and b3a2-b2a2 transcript variants in the three patients, respectively. The results of our study together with a review of literature data suggest that different BCR/ABL transcript variants may occur in CML mimicking ET, without an apparently significant prevalence of one type.
1998
- Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin's lymphomas without symptomatic cryoglobulinemia
[Articolo su rivista]
Luppi, Mario; G., Longo; Mg, Ferrari; Barozzi, Patrizia; Marasca, Roberto; M., Morselli; C., Valenti; Mascia, Maria Teresa; L., Vandelli; D., Vallisa; L., Cavanna; Torelli, Giuseppe
abstract
Background. Epidemiological evidence has suggested an association between hepatitis C virus (HCV) infection and B-cell lymphoproliferation. We studied the prevalence of HCV infection in a series of de novo B-cell non-Hodgkin's lymphoma (B-NHL) cases and correlated virological findings with clinico-histological features. Patients and methods. One hundred fifty-seven patients with de novo B-NHL were included in the study. Their serum was examined by ELISA and RIBA for the presence of anti-HCV antibodies, and either the peripheral blood mononuclear cells or the pathology tissues of all of the patients were examined by reverse transcriptase polymerase chain reaction for the presence of HCV RNA sequences, Results: HCV infection occurred in 22.3% of B-NHL patients and was documented before the diagnosis in about halfof the positive cases. Of interest. HCV infection was more frequently found in follicular center; marginal zone and diffuse large-cell lymphoma types, but was not associated with symptomatic cryoglobulinemia. The median survival time was 48 months in HCV-positive and 52 months in HCV-negative B-NHL patients. Conclusions. Our findings strengthen the pathogenetic link between HCV and B-NHL and show that HCV infection may be associated with the malignant proliferation of defined B-cell subsets other than the immunoglobulin Mk B-cell subset involved in the pathogenesis of mixed cryoglobulinemia type II and associated lymphoplasmacytoid lymphoma type. HCV-related liver disease did not affect the survival of our B-NHL patients.
1998
- Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; R., Garber; Maiorana, Antonino; G., Bonacorsi; T., Artusi; R., Trovato; Marasca, Roberto; Torelli, Giuseppe
abstract
Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA, A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas, 14 Hodgkin's disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 Reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called mummified Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the vines in human lymphomagenesis, The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder.
1998
- Hepatitis C virus genotype distribution in B-Cell non-Hodgkin lymphoma
[Articolo su rivista]
Luppi, Mario; Ferrari, Mg; Torelli, Giuseppe
abstract
No abstract available
1998
- Human herpesvirus 8 seroprevalence in blood donors and lymphoma patients from different regions of Italy
[Articolo su rivista]
D., Whitby; Luppi, Mario; Barozzi, Patrizia; C., Boshoff; Ra, Weiss; Torelli, Giuseppe
abstract
No abstract available
1998
- Integration of human herpesvirus 6 genome in human chromosomes
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Morris, Cm; Merelli, E; Torelli, Giuseppe
abstract
No abstract available
1998
- Might essential thrombocythemia carry Ph anomaly?
[Articolo su rivista]
Marasca, Roberto; Luppi, Mario; Zucchini, Patrizia; Longo, G; Torelli, Giuseppe; Emilia, G.
abstract
Might essential thrombocythemia carry Ph anomaly?
1998
- Occurrence of a novel t(11;19)(q13;q13.3) in complete remission of acute promyelocytic leukemia
[Articolo su rivista]
Temperani, Paola; Luppi, Mario; F., Giacobbi; P., Vaccari; G., Longo; A., Donelli; Narni, Franco; Torelli, Giuseppe; G., Emilia
abstract
A woman with t(15;17) and PML/RAR alpha positive acute promyelocytic leukemia (APL-M3v) achieved a complete remission (CR) with cytogenetic and molecular conversion, after one-month ATRA plus idarubicin treatment. During CR, less than one-month after consolidation therapy with topoisomerase II inhibitors, a novel t(11;19) (q13;q13.3) was detected in peripheral blood stem cells and later in harvest bone marrow cells. Persisting CR and the negativity for BCL1 and PRAD1 genes rearrangement, the autotransplantation was performed, with good outcome. The patient is still in CR eighteen months post-transplant, in spite of the persistence of a small t(11;19) clone in BM cells. The emergence of a novel chromosomal change during CR of acute leukemia is a rare phenomenon. This is the first t(11;19)(q13;q13.3) described in APL. This finding raises the issue of whether the abnormal karyotypes at remission might represent a risk of tumor recurrence. The meaning of this genomic instability is yet unknown.
1998
- Polymerase chain reaction detection of human herpesvirus 8 sequences in primary central nervous system lymphomas
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Marasca, Roberto; Savarino, M; Torelli, Giuseppe
abstract
No abstract available
1998
- Still's disease, severe thrombocytopenia, and acute hepatitis associated with acute parvovirus B19 infection
[Articolo su rivista]
Longo, G; Luppi, Mario; Bertesi, M; Ferrara, L; Torelli, Giuseppe; Emilia, G.
abstract
No abstract available
1997
- Detection of human herpes virus type 8 DNA sequences as a valuable aid in the differential diagnosis of Kaposi's sarcoma
[Articolo su rivista]
Maiorana, Antonino; Luppi, Mario; P., Barozzi; G., Collina; Fano, Rita Adriana; Torelli, Giuseppe
abstract
The occurrence of human herpes virus type 8 (HHV-8) DNA sequences was evaluated by polymerase chain reaction in 36 cases of cutaneous Kaposi's sarcoma (KS) (classic and associated with the acquired immunodeficiency syndrome) and in 88 pathologic entities that can histologically mimic KS, such as reactive and neoplastic vascular processes and lesions featuring focal or extensive spindle cell pattern. A positive reaction was detected in 16 (70%) of 23 samples of classic KS and 10 (77%) of 13 KS cases related to the acquired immunodeficiency syndrome. In particular, 4 (50%) of 8 samples in the patch stage were found to be positive, whereas in the plaque and nodular stages, HHV-8 DNA sequences were observed in 8 (67%) of 12 and 14 (87%) of 16 cases, respectively. KS cases that had yielded previous negative results were found to be positive for HHV-8 on nested polymerase chain reaction, except two cases of classic KS in the patch stage (6% of the total number of KS, 25% of cases in the patch stage). Reactive and neoplastic vascular processes and cutaneous lesions with a spindle cell component were consistently negative, HHV-8 detection by polymerase chain reaction can represent a valuable method for diagnosing KS, particularly in small skin biopsy samples that might show histologic overlap with non-KS lesions, In early patch stage lesions, however, the diagnostic value of the method is hampered by the occurrence of cases in which HHV-8 sequences are still undetectable.
1997
- Hepatitis C virus-induced leuko-thrombocytopenia and haemolysis
[Articolo su rivista]
Emilia, G; Luppi, Mario; Ferrari, Mg; Barozzi, Patrizia; Marasca, Roberto; Torelli, Giuseppe
abstract
Hepatitis C virus (HCV) has been recognized as the cause of thrombocytopenia occurring in patients with chronic hepatitis C, possibly through autoimmune mechanisms. A patient is described with B cell chronic lymphocytic leukaemia, presenting with a marked leuko-thrombocytopenia and an associated mild haemolysis secondary to HCV infection, in the absence of clinical and biochemical signs of hepatitis. Anti-HCV antibodies were detected in the serum both by ELISA and RIBA but not 2 months before the onset of cytopenia. The presence of HCV RNA was documented both in the peripheral blood mononuclear cells and in the bone marrow by reverse transcriptase polymerase chain reaction of the 5´ untranslated region of the viral genome. Of interest, HCV RNA was also found in the serum, showing that viraemia was associated with the presence of circulating anti-HCV antibodies. HCV genotyping, performed by PCR amplification of the core region, revealed the presence of an unclassifiable genotype. The hypothetical mechanisms leading to HCV-induced cytopenia in this patient are briefly discussed. Treatment with corticosteroids was effective in controlling blood cell counts, without increasing viraemia and deterioration of liver disease. HCV infection should be considered in the differential diagnosis of possible causes of cytopenia, mainly in immunosuppressed patients, even in absence of clinical and biochemical signs of hepatitis.
1997
- Human Herpesvirus 8 strain variability in clinical conditions other than Kaposi’s sarcoma
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Marasca, Roberto; Ferrari, Mg; Torelli, Giuseppe
abstract
No abstract available
1997
- Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53
[Articolo su rivista]
F., Kashanchi; J., Araujo; J., Doniger; S., Muralidhar; R., Hoch; S., Khleif; E., Mendelson; J., Thompson; N., Azumi; Jn, Brady; Luppi, Mario; Torelli, Giuseppe; Lj, Rosenthal
abstract
The 357 amino acid open reading frame 1 (OFF-1), also designated DR7, within the SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). Tn the current study, the SalI-L transforming region was localized to the SalI-L-SH subfragment, Several ORFs identified in SalI-L-SH by sequence analysis were cloned into a selectable mammalian expression vector, pBK-CMV, Only pBK/ORF1 transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced fibrosarcomas when injected into nude mice, whereas control cells, expressing either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 protein, were not tumorigenic, Western blot analysis of proteins extracted from the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and the OFF-1 binding domain on p53 was located between residues 28 and 187 of p53, overlapping with the specific DNA binding domain. Functional studies showed that p53-activated transcription was inhibited in ORF-1, but not in truncated OFF-1, expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause transformation. Analysis of several human tumors by PCR revealed OFF-1 DNA sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non-Hodgkin's lymphomas and glioblastomas. The detection of OFF-1 sequences in human tumors, while not proof per se, is a prerequisite for establishing its role in tumor development. Taken together, the results demonstrate that OFF-1 is an HHV-6 oncogene that binds to and affects p53. The identification of both transforming and transactivating activities within ORF-1 is a characteristic of other viral oncogenes and is the first reported for HHV-6.
1997
- Human herpesvirus-6 reactivation in a longitudinal study of two HIV-1 infected patients
[Articolo su rivista]
Iuliano, R; Trovato, R; Lico, S; Luppi, Mario; Forastieri, G; Barsanti, La; Pizzigallo, Am; Mecocci, L; Barozzi, Patrizia; Torelli, Giuseppe; Mazzotta, F; Ceccherininelli, L.
abstract
After primary infection, human herpesvirus-6 (HHV-6) persists in latent form and can be reactivated in immunocompromised subjects. A longitudinal study of HHV-6 infection was carried out in two HIV-1 seropositive patients to provide in vivo evidence of HHV-6 reactivation. Concomitant with a significant rise of anti-HHV-6 IgG detected by IFA, a transient increase of HHV-6 viral load was shown in PBLs by PCR. During HHV-6 reactivation it was also identified either cell-free HHV-6 by PCR in plasma or IgM antibody titers. HHV-6 reactivation was followed by a temporary decrease in CD4+ count and by a progressive dramatic loss of CD4+ during the following 18 months. HHV-6 strain characterization by PCR demonstrated that first patient (MM) initially showed the B variant, followed by reactivation and persistence of the A variant, while in the second (SG) only the A variant was detected. The evidence of HHV-6 reactivation suggests its involvement in immunologic damage underlying the disease.
1997
- Kaposi's sarcoma-associated herpesvirus infection and multiple myeloma
[Articolo su rivista]
Whitby, D; Boshoff, C; LUPPI, Mario; TORELLI, Giuseppe
abstract
No abstract available
1997
- L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release
[Articolo su rivista]
M., Marietta; Facchinetti, Fabio; Neri, Isabella; F., Piccinini; Volpe, Annibale; Torelli, Giuseppe
abstract
..
1997
- Prevalence of HCV infection and second neoplasms in marginal zone lymphomas
[Articolo su rivista]
Luppi, Mario; Longo, G; Ferrari, Mg; Ferrara, L; Marasca, Roberto; Barozzi, Patrizia; Morselli, M; Emilia, G; Torelli, Giuseppe
abstract
No abstract available
1997
- Relationship between BCR/ABL fusion proteins and leukemia phenotype
[Articolo su rivista]
Emilia, G; Luppi, Mario; Marasca, Roberto; Torelli, Giuseppe
abstract
No abstract available
1997
- Sideroblastic anemia terminating in chronic myeloid leukemia
[Articolo su rivista]
Bandieri, E; Didonato, C; Artioli, F; Carapezzi, C; Luppi, Mario; Artusi, T; Torelli, Giuseppe
abstract
No abstract available
1996
- ALPHA-INTERFERON IN THE TREATMENT OF ESSENTIAL THROMBOCYTHEMIA: CLINICAL RESULTS AND EVALUATION OF ITS BIOLOGICAL EFFECTS ON THE HEMATOPOIETIC NEOPLASTIC CLONE.
[Abstract in Rivista]
Sacchi, Stefano; L., Gugliotta; F., Papineschi; A. M., Liberati; S., Rupoli; C., Delfini; M., Ruggeri; L., Cavanna; A., Bucalossi; C., Ferrandina; M., Morselli; Torelli, Giuseppe
abstract
no abstract
1996
- Additional neoplasms and HCV infection in low-grade lymphoma of MALT type
[Articolo su rivista]
Luppi, Mario; Longo, G; Ferrari, Mg; Ferrara, L; Marasca, Roberto; Barozzi, Patrizia; Morselli, M; Emilia, G; Torelli, Giuseppe
abstract
Several chronic inflammatory conditions and genetic alterations are likely to be involved in the pathogenesis of low-grade lymphoma of MALT type. In a well-characterized series of 27 patients with low-grade lymphoma of MALT type, we studied: (1) the incidence of other neoplasms, which might be indicative of genetic instability, apparently a characteristic of this disease; (2) the prevalence of serologic and molecular markers of HCV infection, which has been found in association with other lymphoproliferative disorders. Three patients had one or more additional cancers; a total of eight tumours, five of which occurred in the same patient, suggests the presence of some genetic instability in at least some cases of the disease. Rather unexpectedly, anti-HCV antibodies and HCV RNA sequences were documented in 50% of the patients examined, without elevation of serum transaminases. Of interest, the two patients with parotid and conjunctival MALT lymphomas, respectively, with a previous history of Sjogren's syndrome, were HCV positive. We suggest, for the first time, that HCV may be considered, in addition to Helicobacter pylori, as another potential infectious co-factor in the multistep pathogenesis of low-grade lymphomas of MALT type.
1996
- Frequency and distribution of herpesvirus-like DNA sequences (KSHV) in different stages of classic Kaposi's sarcoma and in normal tissues from Italian population.
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Maiorana, Antonino; G., Collina; M. G., Ferrari; Marasca, Roberto; M., Morselli; E., Rossi; L., Ceccherini Nelli; Torelli, Giuseppe
abstract
The frequency and distribution of herpesvirus-like DNA sequences (KSHV) were investigated by PCR in the pathologic skin lesions of a series of 22 HIV-negative elderly patients with classic Kaposi´s sarcoma (KS) from Italy, one of the few regions of the world where classic KS is prevalent. Viral sequences were clearly identifiable in 15 cases, in particular in 2 of 5 patch, in 3 of 6 plaque and in 10 of 11 nodular lesions. Our findings confirm the association of these herpesvirus-like DNA sequences with KS in unrelated populations, providing evidence of the putative KS-associated agent in all different histologic lesions of the disease, mainly in the nodular stage. The search for other herpesviruses by PCR showed that Epstein-Barr virus (EBV) sequences were present in 7 of 22 pathologic skin lesions. In 4 cases, both EBV and KSHV were present. On the contrary, all 22 classic KS specimens were negative for human herpesvirus-6 sequences. Two of 3 patch and the 1 nodular lesions from AIDS-related KS patients examined were positive for KSHV but negative for both EBV and HHV-6 sequences. Furthermore, we evaluated the prevalence of KSHV sequences in the normal population of the same geographical area. Thirteen peripheral blood mononuclear cell samples, 9 salivary gland tissues and 6 saliva samples from healthy subjects were invariably found negative for KSHV, using the same PCR technique. Of interest, 2 of 11 hyperplastic tonsils harboured these herpesvirus-like sequences, suggesting that, like other herpesviruses, the KS-associated agent may be harboured in a proportion of normal individuals and tonsils may represent at least one of the possible reservoirs of this putative lymphotropic gamma-herpesvirus in vivo.
1996
- HHV-8-associated primary cerebral B-cell lymphoma in HIV-negative patient after long-term steroids
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Marasca, Roberto; Savarino, M; Torelli, Giuseppe
abstract
No abstract available
1996
- Hepatitis C virus infection in subsets of neoplastic lymphoproliferations not associated with cryoglobulinemia
[Articolo su rivista]
Luppi, Mario; Ferrari, Mg; Bonaccorsi, G; Longo, G; Narni, Franco; Barozzi, Patrizia; Marasca, Roberto; Mussini, C; Torelli, Giuseppe
abstract
Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and a dear-cut association has been proposed between HCV infection and mixed cryoglobulinemia (MC), a benign lymphoproliferative disorder, which sometimes evolves into a frank malignant B cell non-Hodgkin's lymphoma (B-NHL). Moreover, the presence of antibodies to HCV, as well as of HCV-specific genomes has been reported in the sera of over 37% patients with B-NHL, not associated with MC. Thus, we decided to perform both a serologic and a molecular study to give insights into a possible relationship between HCV infection and neoplastic lymphoproliferations. We used ELISA and RIBA tests to show that anti-HCV antibodies were present in the serum of 29 out of 69 unselected B-NHL patients (42%), while seropositivity in a healthy population was about 1%. The prevalence of anti-HCV antibodies was low in definite subsets of B lymphoid disorders, including multiple myeloma, Waldenstrom's macroglobulinemia and monoclonal gammopathies of undetermined significance. Then, using reverse transcriptase polymerase chain reaction, we detected HCV sequences directly in the pathologic lymph node biopsies in 13 out of 34 B-NHL cases, and in particular in six out of eight low-grade lymphomas of MALT type and in five out of eight centroblastic-centrocytic follicular lymphomas. In contrast, the peripheral blood samples from 10 B cell chronic lymphocytic leukemia patients resulted negative for the presence of HCV genomes. Similarly, viral sequences were absent in 10 T cell NHL, while only one out of the 14 Hodgkin's disease cases tested resulted positive. Finally, we used a PCR-based assay to characterize the genotypes (I-IV) present in the positive lymphomatous tissues. The presence of both serologic and molecular markers of HCV infection in a high percentage of certain types of B-NHL, not associated with cryoglobulinemia, and its absence from other lymphoproliferative diseases extends the spectrum of HCV-associated lymphoproliferations arguing in favor of some role of this viral infection in the pathogenesis of the malignant proliferation of definite B lymphoid populations.
1996
- Human herpesvirus 8 and interstitial pneumonitis in an HIV-negative patient
[Articolo su rivista]
Luppi, Mario; Torelli, Giuseppe
abstract
No abstract available
1996
- Human herpesvirus-8 DNA sequences in Human Immunodeficiency Virus-negative angioimmunoblastic lymphadenopathy and benign lymphadenopathy with giant germinal center hyperplasia and increased vascularity
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Maiorana, Antonino; T., Artusi; R., Trovato; Marasca, Roberto; M., Savarino; L., Ceccherini Nelli; Torelli, Giuseppe
abstract
Human herpesvirus-8 (HHV-8) DNA sequences have been reported to be strictly associated not only with various forms of Kaposi´s sarcoma but also with an unusual subgroup of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphomas. A possible relation of this putative virus also with multicentric Castleman´s disease (MCD) has been recently suggested. We used polymerase chain reaction to look for the presence of HHV-8 sequences in a well characterized series of benign, atypical, and malignant lymphoid tissues from 45 Hodgkin´s disease and 43 non-Hodgkin´s lymphoma (NHL) cases, as well as from 5 MCD, 15 angioimmunoblastic lymphadenopathy (AILD), and 23 benign lymphadenopathy cases. Among the 38 AIDS-related lymphoid lesions, only 1 NHL and 1 persistent generalized lymphadenopathy (PGL) case were positive. Furthermore, among the 92 non-AIDS-related lymphoproliferative disorders, HHV-8 sequences were detected in 3 classic AILD cases and in 4 reactive lymphadenopathies. Six of 9 HHV-8 positive lymphoid lesions (1 NHL, 1 PGL, 1 AILD, and 3 reactive lymphadenopathy cases) were also positive for Epstein-Barr viral sequences. The four human immunodeficiency virus (HIV) negative lymphadenopathies positive for HHV-8 sequences showed an almost identical histology, characterized by a predominantly follicular lesion, with giant germinal center hyperplasia, and increased vascularity, resembling HIV-related lymphadenopathy and MCD. Our results, while providing the first evidence of the presence of HHV-8 sequences in AILD cases, suggest a possible association of these herpesviral sequences with a distinct hystologic type of non-neoplastic lymphadenopathy, not associated with other common herpes infections.
1996
- Lymphotropic herpes virus (EBV, HHV-6, HHV-8) DNA sequences in HIV negative Castleman's disease
[Articolo su rivista]
Barozzi, Patrizia; Luppi, Mario; Masini, L; Marasca, Roberto; Savarino, M; Morselli, M; Ferrari, Mg; Bevini, M; Bonacorsi, G; Torelli, Giuseppe
abstract
Aim-To evaluate the possible involvement of lymphotropic herpes viruses in Castleman's disease. Methods-Archival formalin fixed, paraffin wax embedded biopsy specimens from 16 HIV negative patients (11 with localised and five of multicentric disease) were studied. Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and human herpes virus-8 (HHV-8) DNA was detected using PCR. PCR was also used to characterise the EBV genomes and the clonal status of the lesions. Results-EBV sequences were identified in nine (56%) cases. The main EBV genotype detected was type 1. Two (12%) cases were positive for both HHV-6 and EBV sequences. HHV-8 sequences were detected in one case of localised Castleman's disease, the sequence of which differed from that of the HHV-8 prototype. No clonal immunoglobulin gene rearrangements were found. Conclusions-EBV DNA was detected in a substantial proportion of cases, suggesting that it may have a role in the pathogenesis of Castleman's disease, unlike HHV-6 which was detected rarely. This is the first report of HHV-8 specific sequences in the localised from of the disease.
1996
- P53 gene mutations in chronic myelogenous leukemia medullary and extramedullary blast crisis
[Articolo su rivista]
Marasca, Roberto; Luppi, Mario; Barozzi, Patrizia; Ferrari, Mg; Morselli, M; Torelli, Giuseppe
abstract
Molecular alterations of the P53 gene were investigated in 27 unselected patients with chronic myelogenous leukemia (CML) blast crisis. A rearrangement of the P53 gene was evident by Southern blotting in 3 cases, one of which also showed the same alteration in the chronic phase. Single strand conformation polymorphism and sequencing analysis showed point mutations in 4 blast crisis cases. Of interest, P53 point mutations were evident in all the 3 cases of extramedullary blast crisis examined and the same point mutation was found in the myeloblastoma tissues and in the subsequent peripheral blast cells. These data indicate that: a) P53 gene mutations occur in a significant but not a large number of CML acute phase cases; b) P53 gene point mutations seem to correlate strongly with the infrequent extramedullary presentation of the blast crisis; c) the presence of the same P53 gene point mutation in extramedullary and bone marrow blast cells confirms the common clonal origin of the two cellular populations.
1996
- Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene
[Articolo su rivista]
Luppi, Mario; Morselli, M; Bandieri, E; Federico, Massimo; Marasca, Roberto; Barozzi, P; Ferrari, Mg; Savarino, M; Frassoldati, A; Torelli, Giuseppe
abstract
Background: Maspin, a recently identified protein related to the family of serpins, is believed to play a role in human breast cancer. In an effort to improve the present methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for maspin transcript to identify small numbers of mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. Patients and methods: Five non-neoplastic mammary tissue samples, 13 breast cancer specimens as well as 17 peripheral blood and 4 bone marrow samples from normal subjects were screened for the presence of maspin mRNA by RT-PCR. The same assay was applied to peripheral blood or bone marrow samples obtained from 29 patients with stages I to IV breast cancer. Results: By RT-PCR it was possible to amplify maspin mRNA in all of the primary and metastatic breast cancer specimens, but in none of the normal hemopoietic samples from healthy donors. Thus, detection of maspin transcript in the peripheral blood or marrow of a patient known to have breast cancer is indicative of the presence of mammary carcinoma cells. In reconstitution experiments, maspin RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear cells (PBMCs). None of the 9 patients with stages I, II, or III breast cancer had maspin transcript in peripheral blood. Of note, 3 of 9 patients with stage TV breast cancer receiving systemic therapy at the time of sample collection, but only I of 11 patients with stage IV not receiving therapy, had detectable maspin transcript in peripheral blood. Moreover, 3 marrow specimens from stage TV patients tested positive by this assay. Conclusions: This pilot study suggests that maspin RT-PCR assay is a sensitive, specific and sufficiently rapid method for detection of small numbers of circulating cells and marrow micrometastases in breast cancer patients. The possibility of applying this assay in the detection of tumor cell contamination of both marrow and stem-cell apheresis harvests of breast cancer patients merits further investigation.
1996
- The new lymphotropic herpesviruses (HHV-6, HHV-7, HHV-8) and hepatitis C virus (HCV) in human lymphoproliferative diseases: An overview
[Articolo su rivista]
Luppi, Mario; Torelli, Giuseppe
abstract
Considerable evidence has been accumulating in favor of a possible involvement of viral agents in the pathogenesis of human lymphomas. The most recent proposal for a lymphoma classification, the Revised European-American Classification, emphasized for the first time the pathogenetic importance of two viruses, namely Epstein-Barr virus (EBV) and human T lymphotropic virus I (HTLV-I) in the development of certain lymphoid neoplasias. However, in the last ten years new viral agents possibly related to lymphoproliferative activity have been discovered: three herpesviruses [human herpesvirus-6 (HHV-6), -7 (HHV-7) and -8 (HHV-8)] and a flavivirus, HCV. HHV-6 was isolated from the peripheral blood of patients with lymphomas and a possible role for this beta-herpesvirus in Hodgkin's disease and in angioimmunoblastic lymphadenopathy (AILD) has emerged from serological and molecular studies. HHV-7, a beta-herpesvirus genetically close to HHV-6, has not yet been found in a human disease but it utilizes CD4 as a receptor on the lymphocyte surface. Only partial HHV-8 genomic sequences have been identified so far, suggesting a genetic homology with members of the gamma-herpesvirus family, including EBV. HHV-8 sequences have been identified for the first time in all forms of Kaposi's sarcoma as well as in a variety of lymphoid disorders, including body-cavity-based non Hodgkin's lymphomas, Castleman's disease, AILD and a type of HIV-negative reactive lymphadenopathy with peculiar histologic features. Finally, after its identification as the major cause of post-transfusion and sporadic non-A, non-B hepatitis, HCV has revealed a lymphotropism both in vitro and in vivo. A strong association between HCV infection and a benign lymphoproliferative disease, essential mixed cryoglobulinemia type II, has clearly emerged both from serological and molecular studies. A possible role for this viral infection in B-cell non Hodgkin's lymphomas not associated with cryoglobulinemia has also been proposed recently. The present work offers an overview of the huge amount of experimental and clinical observations supporting the possible involvement of these new lymphotropic viruses in human lymphoproliferative diseases.
1995
- DETECTION OF PML-RAR-ALPHA FUSION TRANSCRIPT IN PH POSITIVE LEUKEMIA WITH ACUTE PROMYELOCYTIC PHENOTYPE LACKING THE T(15-17) CYTOGENETIC ABNORMALITY
[Articolo su rivista]
Emilia, G; Marasca, Roberto; Longo, G; Ferrari, Mg; Notohamiprodjo, M; Temperani, Paola; Sacchi, Stefano; Torelli, Giuseppe
abstract
A 39-year-old woman was diagnosed with acute promyelocytic leukemia (APL) with disseminated intravascular coagulation syndrome. The hematologic examination showed a morphologic, cytochemical, and immunophenotypic picture typical of an APL, with a marked leukocytosis and a mixed population of hypergranular and microgranular promyelocytes. The cytogenetic analysis showed a 46,XX,t(9;22) karyotype, without any alterations of chromosomes 15 and 17. The t(15;17) translocation was not evident in FISH experiments, while a molecular analysis revealed the presence of a PML-RAR alpha chimera.
1995
- Daily variation of immunoreactive serum interleukin-6 levels in multiple myeloma
[Articolo su rivista]
Bandieri, E.; Luppi, Mario; Luppi, G.; Federico, Massimo; Sabbatini, R.; Torelli, Giuseppe; Piccinini, Lino
abstract
NO ABSTRACT
1995
- HEPATITIS-C VIRUS-INFECTION AND LYMPHOPROLIFERATIVE DISORDERS - RESPONSE
[Articolo su rivista]
Mussini, C; Ghini, M; Mascia, Maria Teresa; Giovanardi, P; Zanni, G; Lattuada, I; Moreali, S; Longo, G; Ferrari, Mg; Torelli, Giuseppe
abstract
In recent years, a high prevalence of both anti-hepatitis C virus (anti-HCV) antibodies (HCVAb) and HCV RNA has been documented in series of patients affected by cryoglobulinemia. The histologic as well as immunocytochemical analysis of the bone marrow of several patients frequently showed the presence of a clear expansioonf a B-lymphocyte population, suggesting a minimal lymphoproliferative disease or al localized immunocytoma ,according to some investigators, may evolve in an overt lymphoma. On the basis of these observations and of the reponed high prevalence of HCV infection markers in Waldenstrom’s macroglobulinemia we analyzed 201 cases of monoclonal gammopathies (MGs) for the presence of HCVAb. The cases were divided in two groups on the basis of the presence or absence of cryoglobulinemic activity. The first group included 94 patients, all affected by type 2 (monoclonal IgMK and polyclonal IgG) cryoglobulinemia, subdivided into) 62 so called “essential” cryoglobulinemias, 12 cryoglobulinemias associated w ith oven lymphoproliferative diseases and 20 cryoglobulinemias associated with autoimmune disorders. Our overall data on 201 patients confirm the strict associatlon between HCV infection and MGs with cryoglobulinemic activity, with the exception of those associated with autoimmune diseases. This relation does not seem to exist with the MGs without cryoglobulinemic activity, such as in MGs of uncertain significance, multiple myeloma, and Waldenstrom’s disease.
1995
- HUMAN HERPESVIRUS-6 - A SURVEY OF PRESENCE AND DISTRIBUTION OF GENOMIC SEQUENCES IN NORMAL BRAIN AND NEUROGLIAL TUMORS
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Maiorana, Antonino; Marasca, Roberto; R., Trovato; Fano, Rita Adriana; L., CECCHERINI NELLI; Torelli, Giuseppe
abstract
In an attempt to study the frequency and distribution of human herpesvirus-6 (HHV-6) infection both in normal and neoplastic brain tissues in vivo, polymerase chain reaction was used to look for HHV-6 genomes: 1) in samples, obtained at necropsy, from different regions of the brain of immunocompetent adult subjects and of patients who died of AIDS; 2) in the surgical biopsies of a well-characterized series of primary brain tumors of neuroglial origin. HHV-6-specific sequences were identified in six of nine brain samples from immunocompetent subjects, and in four of seven brain samples from AIDS patients. Viral sequences were identified in the specimens derived either from the grey (frontal cortex and basal ganglia) or from the periventricular white matter. HHV-6 DNA was found only in 6 of the 37 primary brain tumor biopsies examined. Th is study provides for the first time molecular evidence of a wide distribution of HHV-6 infection in the brain tissues of a high proportion of subjects, both in normal and in impaired immunity. in this large series of tumor biopsies the presence of HHV-6 genomic sequences is a rare phenomenon, arguing against a major role of this herpesvirus in the pathogenesis of primary brain tumors of neuroglial origin in immuno-competent subjects.
1995
- Human herpesvirus-6 genome in acute lymphoblastic leukemia: Evidence against an etiologic relationship
[Articolo su rivista]
Barozzi, Patrizia; Luppi, Mario; Marasca, Roberto; Trovato, R; Ceccherininelli, L; Torelli, Giuseppe
abstract
No abstract available
1995
- MONOCLONAL GAMMOPATHIES AND HEPATITIS-C VIRUS-INFECTION
[Articolo su rivista]
Mussini, C; Ghini, M; Mascia, Maria Teresa; Giovanardi, P; Zanni, G; Lattuada, I; Moreali, S; Longo, G; Ferrari, Mg; Torelli, Giuseppe
abstract
we analyzed 201 cases of monoclonal gammopathies for the prevalence of HCV Ab. The cases were divided in two groups on the presence or absence of cryoglobulinemic activity.The first group included 94 patients all affected by type II cryoglobulinemia ( 62 "essential" mixed cryioglobulinemia, 12 overt lymphoproliferative diseases 20 autoimmune diseases ) ; the second group included 107 subjects (MGUS,myeloma, Waldestrom disease, immunocytoma ) without cryoglobulinemic activity. We found a very high prevalence of HCVAb in "essential" mixed cryoglobulinemia and in lymphoproliferative diseases ( 83%) whereas no strict relation was found between HCV infection a cryoglobulinemias secondary to autoimmune diseases ( 15%). In MGs without cryoglobulinemic activity the prevalence od HCVAb was very low. Our data confirm the strict association between HCV infection and MGs with cryoglobulinemic activity, with the exception of those associated with autoimmune diseases.
1995
- P53 GENE POINT MUTATIONS IN RELATION TO P53 NUCLEAR-PROTEIN ACCUMULATION IN COLORECTAL CANCERS
[Articolo su rivista]
Costa, A; Marasca, Roberto; Valentinis, B; Savarino, M; Faranda, A; Silvestrini, R; Torelli, Giuseppe
abstract
It is known that structural alterations of the p53 tumour suppressor gene cause malignant transformation and tumour progression in colorectal mucosa. In this study, 38 colorectal cancers were analysed for mutations detected in the p53 gene by single-strand conformational polymorphism and DNA sequence analysis, and the results were compared with p53 protein expression detected by immunohistochemistry. A very strict association (P<0.0001) was found between genetic alterations and protein accumulation, as detected by the PAb 1801 monoclonal antibody. p53 expression and gene mutations were more frequent in rectal than in colonic cancers. No relation was observed with Dukes' stage, even though most of the mutations were at exon 7 in Dukes' A-B cancers and almost all mutations at exon 8 were observed in Dukes' C-D cancers. DNA ploidy was not generally associated with p53 protein expression or gene mutations. However, 83 per cent of cases with exon 5 and 6 mutations were diploid or near-diploid and 71 per cent of cases with mutations at exons 7 and 8 were aneuploid. Tumours with p53 gene mutations at exon 5 had a higher median [H-3]thymidine labelling index (17 per cent) than those with mutations at exons 6, 7, and 8 (11.8 per cent).
1995
- Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo
[Articolo su rivista]
Torelli, Giuseppe; Marasca, Roberto; Paola, Cocconcelli; Elisa, Merelli; Luca Ceccherini, Nelli; Ferrari, Sergio; Mario, Luppi; Barozzi, Patrizia
abstract
Out of 64 cases of non-Hodgkin's lymphomas (NHL), 55 cases of Hodgkin's disease (HD) and 31 cases of multiple sclerosis (MS), 2 NHL, 7 HD and 1 MS cases were found positive by polymerase chain reaction (PCR) for the presence of HHV-6 sequences in pathologic lymph nodes of the lymphomas and in peripheral blood mononuclear cells (PBMCs) of MS. A further analysis of the PBMCs of the PCR positive cases by standard Southern blot technique revealed only 2 NHL, 3 HD and 1 MS cases as positive, indicating that these six patients have an unusually high viral copy number in the PBMCs. Restriction analysis, carried out using probes representative of different regions of the virus, showed that three cases retain only a deleted portion of the viral genome. In the remaining three cases a complete viral genome was present, containing the right end sequences in which the rep-like gene, possibly crucial to the viral and cellular life cycle, is located. The analysis by pulsed field gel electrophoresis (PFGE) of the total DNA of the PBMCs obtained directly, without culture from PBMCs of these last three cases (1 NHL, 1 HD, and 1 MS), using the same probes, showed the absence of free viral molecules and the association of viral sequences with high molecular weight DNA. These results are consistent with in vivo integration of the entire virus in the cellular genome. A further study of the same patients with chromosome fluorescence in situ hybridization (FISH) showed in all the three cases the presence of a specific hybridization site, located at the telomeric extremity of the short arm of chromosome 17 (17p13), suggesting that this location is at least a preferred site of an infrequent, but possibly biologically important, integration phenomenon.
1994
- Clonal nature of hypereosinophilic syndrome
[Articolo su rivista]
Luppi, Mario; Marasca, Roberto; Morselli, M; Barozzi, Patrizia; Torelli, Giuseppe
abstract
No abstract available
1994
- DOUBLE P53 POINT MUTATION IN EXTRAMEDULLARY BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA
[Articolo su rivista]
Marasca, Roberto; Longo, G; Luppi, Mario; Barozzi, Patrizia; Torelli, Giuseppe
abstract
A patient with Philadelphia-positive chronic myelogenous leukemia (CML) evolved in extra-medullary blast crisis, was studied for the presence of alterations of the P53 tumor suppressor gene in the different stages of disease progression. No P53 gene aberrations were detected during the chronic and accelerated phases. Two identical missense point mutations, involving codons 249 and 281 and leading to the amino acid substitutions Arg-Ser and Thy-Asp, were identified in cells of an extramedullary mass and then in peripheral blood blast crisis cells. The data indicate that the medullary and extramedullary blast cells belong to the same cellular clone. They also strongly suggest that in this case, the alteration of P53 gene is strictly related to the progression of the disease, although this mechanism is certainly neither the only nor the most frequent molecular event leading to the acute phase.
1994
- Human herpesvirus 6 infection in normal human brain tissue
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Maiorana, Antonino; Marasca, Roberto; Torelli, Giuseppe
abstract
No abstract available
1994
- INTEGRATION OF HUMAN HERPESVIRUS-6 (HHV-6) GENOME IN CHROMOSOME-17 IN 2 LYMPHOMA PATIENTS
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Marasca, Roberto; Torelli, Giuseppe
abstract
No abstract available
1993
- 3 CASES OF HUMAN HERPESVIRUS-6 LATENT INFECTION - INTEGRATION OF VIRAL GENOME IN PERIPHERAL-BLOOD MONONUCLEAR CELL-DNA
[Articolo su rivista]
Luppi, Mario; Marasca, Roberto; Barozzi, Patrizia; Ferrari, Sergio; Ceccherininelli, L; Batoni, G; Merelli, E; Torelli, Giuseppe
abstract
Saliva and peripheral blood mononuclear cells from three patients, two with lymphoproliferative disorders and one suffering from multiple sclerosis, were examined for the presence of human herpesvirus-6 (HHV-6) genome by using the polymerase chain reaction and Southern blot analysis. The search for anti-HHV-6 antibodies, carried out in the sera of the same cases by an immunofluorescence assay, was negative in two cases at the lowest dilution used (1:40). These three patients had a high number of HHV-6 specific sequences in uncultured peripheral blood mononuclear cells, which are thought to be a normal site of viral latency although, in healthy individuals, the infected cells are extremely rare. In order to gain some insight into the state of the viral genome in this latent HHV-6 infection, we used pulsed field gel electrophoresis to separate HHV-6 DNA directly from HHV-6 (strain GS) infected HSB-2 cells and from the peripheral blood mononuclear cells of these three patients. Our study showed the presence of intact viral genome, of the expected length of 170 kb, persisting as free extrachromosomal element in the HSB-2 cells but not in patients' peripheral blood mononuclear cells. On the other hand, in strong contrast with the results obtained in infected HSB-2 DNA, the restriction analysis of the three patients' peripheral blood mononuclear cell DNA showed fragments of molecular weight constantly higher than the 170 kb segment, indicating that the viral sequences are linked to high molecular weight cellular DNA. Our findings are consistent only with a latent infection in which HHV-6 is integrated in vivo and suggest that pulsed field gel electrophoresis analysis is well worth using to evaluate the presence of integrated, intact, or fragmented viral genomes in HHV-6 associated lymphoproliferative diseases and immune disorders.
1993
- CHARACTERIZATION OF HUMAN HERPESVIRUS-6 GENOMES FROM CASES OF LATENT INFECTION IN HUMAN LYMPHOMAS AND IMMUNE DISORDERS
[Articolo su rivista]
Luppi, Mario; Barozzi, Patrizia; Marasca, Roberto; Ceccherininelli, L; Torelli, Giuseppe
abstract
No abstract available
1993
- FAILURE TO DETECT GENOMIC MATERIAL OF HTLV-I OR HTLV-II IN MONONUCLEAR-CELLS OF ITALIAN PATIENTS WITH MULTIPLE-SCLEROSIS AND CHRONIC PROGRESSIVE MYELOPATHY
[Articolo su rivista]
Merelli, E; Sola, P; Marasca, Roberto; Salati, R; Torelli, Giuseppe
abstract
To contribute to the undecided question if a retrovirus of the human T-cell lymphotropic virus (HTLV) family may be involved in the development of multiple sclerosis (MS), we investigated by the polymerase chain reaction (PCR) the presence of HTLV-I and HTLV-II sequences in the peripheral blood mononuclear cell DNAs from 30 patients affected by MS and 15 by chronic progressive myelopathy. Moreover a control group of 14 blood donors was examined. All these patients were devoid of anti-HTLV-I antibody in the serum and cerebrospinal fluid at ELISA. For the PCR, primers and probes, specific for the tax region common to HTLV-I and HTLV-II, for the pol region of HTLV-I, and for the pol region of HTLV-II were used. In spite of the high sensitivity of the technique used, the three groups of subjects were negative for HTLV-I and HTLV-II genomic sequences.
1993
- FREQUENT DETECTION OF HUMAN HERPESVIRUS-6 SEQUENCES BY POLYMERASE CHAIN-REACTION IN PARAFFIN-EMBEDDED LYMPH-NODES FROM PATIENTS WITH ANGIOIMMUNOBLASTIC LYMPHADENOPATHY AND ANGIOIMMUNOBLASTIC LYMPHADENOPATHY-LIKE LYMPHOMA
[Articolo su rivista]
Luppi, Mario; Marasca, Roberto; Barozzi, Patrizia; Artusi, T; Torelli, Giuseppe
abstract
In search of a possible involvement of viral agents in angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) and AILD-like lymphoma (AILD-L), we studied the presence of human herpesvirus-6 (HHV-6) in the lymph node biopsies of 12 cases by polymerase chain reaction (PCR). Given the rarity of this lymphoproliferative disorder, we investigated archival specimens, consisting of formalin-fixed and paraffin-embedded tissues, obtained from patients with a clinical and histologic diagnosis of AILD and AILD-L. HHV-6 sequences were detected in the lymph node biopsies of 7 out of the 12 AILD and AILD-L cases examined. HHV-6 sequences were identified also in the involved liver and spleen tissues of one patient and in the PBMCs of two patients, all carrying viral sequences in the affected lymph nodes. We also used PCR to characterize the HHV-6 genomes, showing that two different viral strains are represented in the pathologic tissues. This study provides evidence of the presence of HHV-6 specific sequences in an unexpectedly high proportion of our series of AILD and AILD-L cases, suggesting a possible involvement of this lymphotropic virus in the pathogenesis of at least some cases of the disease.
1993
- HUMAN HERPESVIRUS-6 AND MULTIPLE-SCLEROSIS - SURVEY OF ANTI-HHV-6 ANTIBODIES BY IMMUNOFLUORESCENCE ANALYSIS AND OF VIRAL SEQUENCES BY POLYMERASE CHAIN-REACTION
[Articolo su rivista]
Sola, P; Merelli, E; Marasca, Roberto; Poggi, M; Luppi, Mario; Montorsi, M; Torelli, Giuseppe
abstract
A possible involvement of human herpesvirus 6 (HHV-6) infection in the pathogenesis of multiple sclerosis (MS) was investigated. The immunofluorescence analysis of sera from 126 MS patients showed significantly higher anti-HHV-6 antibody titres in MS sera than in 500 normal controls. A polymerase chain reaction (PCR) assay of the peripheral blood mononuclear cell (PBMC) DNAs of 31 MS patients and 24 normal subjects was positive in one normal control and in one MS patient. The Southern blot analysis indicated an unexpectedly high level of viral sequences in the MS patient, but not in the control. Since viral sequences are rarely present in MS subjects, the high anti-HHV-6 antibody titres found in MS are likely to be related to immune impairment rather than reactivation of a latent infection.
1992
- Bcl-2 gene expression in hematopoietic cell differentiation.
[Articolo su rivista]
M. T., Mariano; Moretti, Luigi; A., Donelli; M., Grantini; Montagnani, Giuliano; DI PRISCO, Alfredo Ubaldo; Torelli, Giuseppe; Torelli, Umberto; Narni, Franco
abstract
The expression of bcl-2 appears to be typical ofcertain lymphoid malignancies. High levels of bcl-2 mRNAhad been found, previously, in established pre-B-cell lines.However, in fresh specimens, the peak level of bcl-2 expressionshifts to a more differentiated cell type, represented bythe long-living B lymphocytes that are found in most cases ofchronic lymphocytic leukemia. bcl-2 gene product might havea role in prolonging cell survival and, even in the absence oftranslocations, might contribute to some of the biologicfeatures that are typical of this disorder.
1992
- HUMAN HERPESVIRUS-6 IN NON-AIDS RELATED HODGKINS AND NON-HODGKINS-LYMPHOMAS
[Articolo su rivista]
Torelli, Giuseppe; Marasca, Roberto; Montorsi, M; Luppi, Mario; Barozzi, Patrizia; Ceccherini, L; Batoni, G; Bendinelli, M; Muyombano, A.
abstract
Human herpesvirus 6 in non-AIDS related Hodgkin's and non-Hodgkin's lymphomas.
1992
- In vitro transformation by HHV-6 (Human Herpes-virus 6)
[Articolo su rivista]
G., Batoni; R., Trovato; F., Lojacono; L. A., Barsanti; M., Morelli; P., Barozzi; Luppi, Mario; Maiorana, Antonino; Torelli, Giuseppe; L., Ceccherini Nelli
abstract
The in-vitro transformation by human herpesvirus 6 is described
1992
- LYMPHOCYTES AND LOW-FREQUENCY ELECTROMAGNETIC-FIELDS
[Articolo su rivista]
Cadossi, R; Bersani, F; Cossarizza, Andrea; Zucchini, P; Emilia, G; Torelli, Giuseppe; Franceschi, C.
abstract
Human lymphocytes have been used by several researchers to investigate the biological effect of electromagnetic fields (EMF). EMF modulate the response by lymphocytes to lectin stimulation. The size and direction of the effect depends both on the lymphocyte physiology and on the physical parameters characterizing the EMF. Lymphocytes have also been used to investigate the genotoxicity of EMP exposure.
1992
- Proliferation, Differentiation Arrest, and Survival in Leukemic Blast Cells
[Articolo su rivista]
Ferrari, S.; Manfredini, R.; Grande, A.; Torelli, G.; Torelli, U.
abstract
1991
- EFFECT OF LOW-FREQUENCY LOW-ENERGY PULSING ELECTROMAGNETIC-FIELDS ON MICE INJECTED WITH CYCLOPHOSPHAMIDE
[Articolo su rivista]
Cadossi, R; Zucchini, P; Emilia, G; Franceschi, C; Cossarizza, Andrea; Santantonio, M; Mandolini, G; Torelli, Giuseppe
abstract
C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy. The grafting efficiency of the bone marrow was evaluated by examining the number of spleen colonies and the spleen and bone marrow labeling indices at day 8; all parameters proved to be significantly lower among mice grafted with the bone marrow of mice injected with CY and exposed to PEMF than among controls injected with CY only. Finally, we found that the effect of PEMF is evident only if mice are exposed during the 24 h following CY injection. The data reported here indicates that PEMF exposure after CY injection increases the damage induced in mice by CY.
1991
- HHV-6 INFECTION AND HUMAN HODGKIN AND NON-HODGKIN LYMPHOMAS
[Articolo su rivista]
Torelli, Giuseppe; Marasca, Roberto; Selleri, L; Luppi, Mario; Montorsi, M; Federico, Massimo; Narni, Franco; Ceccherininelli, L; Ferrari, Sergio
abstract
1991
- Human Herpes virus-6 in human lymphomas: identification of specific sequences in Hodgkin's lymphomas by polymerase chain reaction
[Articolo su rivista]
Torelli, Giuseppe; Marasca, Roberto; Luppi, Mario; L., Selleri; Ferrari, Sergio; Narni, Franco; Mt, Mariano; Federico, Massimo; L., CECCHERINI NELLI; M., Bendinelli; G., Montagnani; M., Montorsi; Artusi, Tullio
abstract
In search of a possible involvement of the human herpesvirus type 6 (HHV-6) in human Hodgkin's and non-Hodgkin's lymphomas, we studied the levels of anti-HHV-6 antibodies in the sera of 94 cases by an immunofluorescence assay, as well as the presence of HHV-6 sequences in the affected tissues of 66 cases by polymerase chain reaction, using one set of primer oligonucleotides. Our results showed higher anti-HHV-6 antibody titers in human lymphomas than in normal blood donors, but the difference is statistically significant only when normal donors are compared with Hodgkin's lymphoma cases. HHV-6 sequences were detected in 3 of 25 Hodgkin's lymphomas and 0 of the 41 cases of non-Hodgkin's lymphomas studied. The three cases positive for HHV-6 sequences belong to the nodular sclerosis-lymphocyte depletion histologic subtype and share remarkable similarities in their clinical features. Furthermore, Southern blot analysis of total genomic DNA obtained from the neoplastic tissues of two of the three patients showed the same restriction fragment length polymorphism. Our results suggest that: (1) the high level of anti-HHV-6 antibodies in Hodgkin's disease is due to an activation of the immune system not related to the presence of HHV-6 sequences in affected lymph nodes; (2) the presence of HHV-6 sequences in human lymphoid tissues is not a frequent event, rather it is in fact a very rare event in non-Hodgkin's lymphomas, while in Hodgkin's cases it is more frequent than previously reported on the basis of Southern blot analysis; and (3) the presence of HHV-6 sequences in Hodgkin's lymphomas may have a relation with the clinical presentation of the disease.
1990
- Extramedullary pleural blast crisis in chronic myelogenous leukemia: cytogenetic and molecular study.
[Articolo su rivista]
Sacchi, Stefano; Temperani, P; Selleri, L; Zucchini, P; Morselli, S; Vecchi, A; Longo, R; Torelli, Giuseppe; Emilia, G; Torelli, U.
abstract
two patients with Ph1-positive chronic myelogenous leukemia with pleural blastic transformation occurring before medullary involvement are presented. The clonal origin of the pleural cells identified as unclassified blasts in 1 patient and as erythroid blasts in the other was confirmed by the presence of the t(9;22) translocation and their clonal evolution by the presence of duplicated Ph1 and additional chromosome alterations. DNA obtained from the pleural blasts and peripheral blood cells of 1 patient showed an identically rearranged bcr configuration, indicating the origin of the pleural blasts from the CML clone and suggesting that this genomic event is not directly linked with the progression of disease.
1990
- Ratios between the abundance of messenger RNA and the corresponding protein of two growth-related genes, c-myc and vimentin, in leukemia blast cells..
[Articolo su rivista]
Ferrari, S; Tagliafico, Enrico; D'Incá, M; Ceccherelli, G; Manfredini, R; Selleri, L; Donelli, A; Sacchi, Stefano; Torelli, Giuseppe; Torelli, U.
abstract
The abundance of the mRNAs of two growth-related genes, vimentin and c-myc, and that of the corresponding proteins have been studied in unstimulated and phytohemagglutinin-stimulated lymphocytes as well as in 18 populations of leukemic blast cells. The quantitative assay was carried out by densitometric scanning of Northern and Western blots. In normal lymphocytes the mRNA and the protein of both genes were almost undetectable. The phytohemagglutinin stimulation led to a sharp increase of the mRNA and the proteins of vimentin and c-myc. The increase was followed by a progressive fall of the gene products. The rate of decrease of the two mRNAs was similar to that of the corresponding proteins. In some leukemic populations very similar amounts of the vimentin protein were accompanied by amounts of the mRNA differing at least 25 times. Not unlikely, very similar amounts of p62c-myc corresponded to mRNA abundances differing at least 16 times. The coordinated biogenesis of both messenger RNAs and proteins, which occurs in mitogen-stimulated lymphocytes, is substituted, in approximately 30% of the leukemic blast cell populations, by molecular events leading to the accumulation of an excess of mRNA.
1990
- SURVEY OF THE PRESENCE OF ANTI-HHV6 ANTIBODIES AND HHV6 SEQUENCES IN NON-HODGKIN LYMPHOMA CASES
[Articolo su rivista]
Selleri, L; Marasca, Roberto; Luppi, Mario; Montorsi, M; Ceccherininelli, L; Bendinelli, M; Torelli, Giuseppe
abstract
1989
- "Biologia molecolare delle leucemie e dei linfomi: Biologia molecolare della cellula, citogenetica e genetica molecolare
[Monografia/Trattato scientifico]
Torelli, Umberto; Emilia, Giovanni; Torelli, Giuseppe; Ferrari, Sergio; Narni, Franco
abstract
L'applicazione delle tecniche del DNA ricombinante allo studio delle leucemie e dei linfomi ha permesso di approfondire la conoscenza dei meccanismi molecolari dei processi mielo- e linfo-proliferativi, di valutarne il significato prognostico e di aprire nuove prospettive di terapia mirata. Gli autori raccolgono in questa rassegna i dati più significativi emersi degli studi condotti in questo in settore in costante aggiornamento.
1989
- Cytogenetic and molecular studies in primary myelofibrosis
[Articolo su rivista]
Emilia, G.; Temperani, P.; Ferrari, S.; Zucchini, P.; Tagliafico, E.; Selleri, L.; Torelli, G.; Artusi, T.; Torelli, U.
abstract
Cytogenetic and molecular data of three patients affected by primary myelofibrosis with myeloid metaplasia (PMMM) evolving to blastic crisis are reported. The cytogenetic findings were uncommon. The first patient (female) showed an idic(X)(q13) as the sole alteration in chronic phase, with an additional r(7) in 67% of the cells of the blast crisis; the other two patients showed, in blast crisis, a partial trisomy of the long arm of chromosome 1, without translocation, as a unique structural abnormality. These findings confirm the presence of nonrandom, although nonspecific, alterations in PMMM that, in our cases, seem to be related to the multistep progression of the neoplastic process. Molecular investigations have been applied to study the genomic organization and the level of expression of genes such as bcr and calcyclin and c-fms protooncogene possibly involved in the molecular mechanisms underlying cell proliferation in hematopoietic cells. The data obtained are discussed with respect to the myeloproliferative disorder. © 1989.
1989
- Effect of low frequency low energy pulsing electromagnetic field (PEMF) on x-ray-irradiated mice
[Articolo su rivista]
Cadossi, R.; Hentz, V. R.; Kipp, J.; Eiverson, R.; Ceccherelli, G.; Zucchini, P.; Emilia, G.; Torelli, G.; Franceschi, C.; Cossarizza, A.
abstract
C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PEMF 24 h a day, we observed a more rapid decline in white blood cells (WBC) in the peripheral blood of mice exposed to PEMF at all the x-ray dosages used. No effect of exposure to PEMF was observed on the survival of the mice irradiated with 6.3 Gy and 8.5 Gy; in mice irradiated with 6.8 Gy, 2 out of 12 survived when exposed to PEMF as compared to 10 out of 12 control mice that were irradiated only. At day 4 after irradiation autoradiographic studies performed on bone marrow and spleen of 8.5-Gy-irradiated mice showed no difference between controls and mice exposed to PEMF, whereas on 6.8-Gy mice the bone marrow labeling index was lower in mice exposed to PEMF. In mice irradiated to 6.3 Gy we observed that the recovery of WBC in the peripheral blood was slowed in the mice exposed to PEMF and their body weight was significantly lower than in control mice that were irradiated only. The spleen and bone marrow of the mice irradiated to 6.3 Gy and sacrificed at days 4, 14, 20, and 25 after irradiation were analyzed by autoradiography to evaluate the labeling index. Half of the spleens from mice sacrificed at day 25 after irradiation were used to evaluate the RNA content. Autoradiography showed that in the spleen and bone marrow of control mice, there were more cells labeled with [3H]thymidine at days 4 and 14 and less at days 20 and 25 after irradiation in comparison with mice irradiated and exposed to PEMF. The Northern blot analysis of histone H3 and p53 protein RNAs extracted from the spleens at day 25 after irradiation showed a slight increase in cycling cells among spleens of mice exposed to PEMF. We suggest that the exposure of PEMF immediately after x-ray irradiation results in increased damage.
1989
- Expression of the myeloperoxidase gene in acute and chronic myeloid leukemias: relationship to the expression of cell cycle-related genes.
[Articolo su rivista]
Ferrari, Sergio; Tagliafico, Enrico; Ceccherelli, G; Selleri, L; Calabretta, Bruno; Donelli, A; Temperani, Paola; Sarti, M; Sacchi, Stefano; Emilia, Giovanni; Torelli, Giuseppe; Torelli, Umberto
abstract
The expression of the myeloperoxidase (MPO) gene was studied, by means of Northern blot analysis in 14 cases of acute myeloid leukemia (AML), 11 cases of chronic myeloid leukemia (CML), and 6 cases of CML blast crisis, and in HL60 cells before and after induction of terminal differentiation with retinoic acid (RA), phorbol esters (TPA), or vitamin D. The expression of a panel of cell cycle-related genes, namely C-MYC, histone H3, ornithine decarboxylase, P53, vimentin, and calcyclin, was also studied in the same cell populations. Our results indicate that: (a) MPO gene expression (steady state mRNA levels) is strictly confined to the first stages of myeloid differentiation, reaching its peak at the promyelocyte stage and becoming undetectable in mature granulocytes and monocytes; (b) cells devoid of any detectable MPO enzymatic activity such as leukemic basophils have a high content of MPO mRNA; and (c) MPO gene expression is not related to the growth activity of the cell population. Finally, our results show that the pattern of expression of growth-regulated genes in the neoplastic myeloid disorders AML, CML, and CML blast crisis is remarkably different.
1989
- Philadelphia-positive chronic myelogenous leukemia with typical bcr/abl molecular features and atypical, prolonged survival
[Articolo su rivista]
Selleri, L.; Emilia, G.; Temperani, P.; Grassilli, E.; Zucchini, P.; Tagliafico, E.; Bonati, A.; Venezia, L.; Ferrari, S.; Torelli, U.; Torelli, G.
abstract
Despite the major breakthrough in the knowledge of the molecular events underlying the t(9;22) translocation, still no consistent data have been found on the evolution of Ph1 positive CML from the chronic to the accelerated or blastic phase of the disease. In most patients in fact the bcr/abl rearrangements are identical both in chronic phase and in blast crisis, and overall differences in chronic phase duration, related to different location of breakpoints inside the bcr region, were found to be marginal. We approached this problem by studying the molecular features of the bcr/abl abnormality in rare CML patients with very long, atypical chronic phase. The three patients studied, whose chronic phase duration is 17, 19, and 21 years, respectively, have typical genomic bcr rearrangements, and two of them show, hybridizing Northern blots to c-abl, the 8.5 kb mRNA, as that typically present in CML. It seems that genomic alterations within bcr and abl cannot account, alone, for the duration of the chronic phase of Ph1 positive CML and those quantitative and/or qualitative alterations of the p210 bcr/abl protein, unluckily awkward to prove, might be responsible for the atypical clinical features of these CML long survivors.
1989
- T cell receptor genes expression in B cell leukaemias.
[Articolo su rivista]
Narni, Franco; M. T., Mariano; A., Col; M., Grantini; F., Merli; A., Donelli; G., Montagnani; DI PRISCO, Alfredo Ubaldo; Torelli, Giuseppe; Torelli, Umberto
abstract
Using Northern-blot analysis we have studied theexpression of T-cell receptor (TCR) a, b and y chain genes inprimary cells obtained from 36 leukaemic patients. Fifteenpatients had myeloid leukaemias, two had T-cell leukaemias,and 19 leukaemias corresponding to various stages of Blymphocyte differentiation. We observed that truncated TCRbeta mRNAs were produced in B-cells at relatively high levelseven in the absence of detectable gene rearrangements. Ti alfa mRNAs of abnormal size were also frequently found. Suchtranscripts were not detectable in total RNA extracted fromleukaemic myeloid cells. Factors allowing Ti alfa and beta genetranscription must be active in leukaemic pre-B and B cellsbut not in myeloid cells. Neither B-lineage nor myeloidleukaemias expressed TCR y gene at detectable levels.
1988
- Expression of oncogenes and cell cycle related genes in acute and chronic leukemias.
[Articolo su rivista]
Ferrari, Sergio; Calabretta, Bruno; Selleri, L; Ceccherelli, G; Torelli, Giuseppe; Torelli, Umberto
abstract
The authors have assayed the level of expression of several cell-cycle related genes in several populations of circulating myeloid leukemic blast cells. The genes explored included oncogenes such as c-myc, c-myb, p53, and cell-cycle-related genes such as vimentin, calcyclin, ornithine decarboxylase (ODC) and histone H3. Particular attention was given to analysis of the relationship existing between the mRNA levels of the histone H3 gene, which is expressed specifically in the S phase of the cell cycle, and the levels of other genes that are expressed in different stages of the G1 phase. Remarkable differences were observed among the different cases indicating that a differential expression of cell-cycle-related genes characterizes many acute leukemias. This differential expression is reflected in an altered ratio among G1-related genes and the H3 histone gene. The large fraction of leukemic cells which does not express histone H3 and therefore is functionally noncycling, shows a heterogeneous pattern of G1-related gene expression. This reflects the inability of most leukemic cells to progress through the G1 phase into the S phase of the cell cycle. This inability represents an abnormality of the cell cycle. It is concluded that the study of the expression of cell-cycle genes and protooncogenes in in understanding how leukemic cells enter a state of proliferation arrest, which appears to occur in a large fraction of leukemic cells.
1988
- Myeloperoxidase gene expression in blast cells with a lymphoid phenotype in cases of acute lymphoblastic leukemia.
[Articolo su rivista]
Ferrari, Sergio; M. T., Mariano; Tagliafico, Enrico; M., Sarti; G., Ceccherelli; L., Selleri; F., Merli; Narni, Franco; A., Donelli; Torelli, Giuseppe
abstract
By using a cDNA clone of the myeloperoxidase (MPO) gene, we have studied, by Northern blot analysis, the level of MPO mRNA in eight cases of acute lymphoblastic leukemia (ALL). The blast cell populations studied were characterized by morphologic, cytochemical, immunochemical, and molecular criteria. With all the methods used the populations were found to be highly homogeneous and showed a typical lymphoid phenotype. In particular, the Ig heavy-chain gene rearrangement was largely prevalent, and the germ line configuration was almost absent. However, in three of eight cases, high levels of MPO mRNA were detected. The remarkable homogeneity of the cell populations examined suggests that the MPO mRNA observed was present in cellular elements certainly identified as lymphoid. The absence of contamination by myeloid cells was confirmed by the results of Western blot analysis of the proteins of the cell population studied: no MPO protein was detectable. The levels of mRNA observed were high enough to be comparable to those observed in a promyelocytic cell population.
1988
- The effects of low frequency pulsing electromagnetic fields on the response of human lymphocytes to lectins. Changes at different values of induced electrical tension
[Abstract in Rivista]
Cadossi, R.; Ceccherelli, G. B.; Emilia, G.; Torelli, G.; Ruggieri, M. P.; Bersani, F.; Cossarizza, A.; Franceschi, C.
abstract
Lymphocytes obtained from the periferal blood of normal donors and patients suffering from B-chronic lymphocytic leukemia (B-CLL) were cultured. Lymphocyte cultures containing phytohemagglutinin (PHA) were exposed to low frequency pulsing electromagnetic fields (PEMFs). An increase in cell proliferation was observed when relatively "low" amplitude electromagnetic fields were used. By increasing the amplitude of the electromagnetic field, a reversal effect was obtained and inhibition of lymphocyte proliferation was observed. Lymphocyte cultures exposed to low amplitude PEMFs showed increased cell proliferation also when cultured in the presence of sub-optimum concentrations of PHA. Data are presented showing that in consequence of PEMF exposure more B-cell soluble growth factors are found in the culture medium. © 1988.
1988
- The effects of low frequency pulsing electromagnetic fields on the response of human lymphocytes to lectins. Changes at different values of induced electrical tension
[Abstract in Rivista]
Cadossi, R.; Ceccherelli, G. B.; Emilia, G.; Torelli, G.; Ruggieri, M. P.; Bersani, F.; Cossarizza, A.; Franceschi, C.
abstract
Lymphocytes obtained from the periferal blood of normal donors and patients suffering from B-chronic lymphocytic leukemia (B-CLL) were cultured. Lymphocyte cultures containing phytohemagglutinin (PHA) were exposed to low frequency pulsing electromagnetic fields (PEMFs). An increase in cell proliferation was observed when relatively "low" amplitude electromagnetic fields were used. By increasing the amplitude of the electromagnetic field, a reversal effect was obtained and inhibition of lymphocyte proliferation was observed. Lymphocyte cultures exposed to low amplitude PEMFs showed increased cell proliferation also when cultured in the presence of sub-optimum concentrations of PHA. Data are presented showing that in consequence of PEMF exposure more B-cell soluble growth factors are found in the culture medium. © 1988.
1987
- Establishment and characterization of a human IgA-kappa-secreting plasma cell line (MT3).
[Articolo su rivista]
Donelli, A; Narni, Franco; Tabilio, A; Emilia, Giovanni; Selleri, L; Colo, A; Zucchini, Patrizia; Montagnani, Giuliano; Torelli, Giuseppe; Torelli, Umberto
abstract
We have established a new human plasma cell line from the peripheral blood of a patient with an IgA-kappa plasma-cell leukemia. Morphological, immunological, cytogenetic and molecular studies confirm that the cultured cells are derived from the same clone of leukemic plasma cell in vivo. The established cell line (MT3) grows in suspension, secretes high amounts of IgA kappa and exhibits morphological and ultrastructural characteristics of plasma cells. Surface marker analysis shows that both primary and cultured cells express the plasma-cell-associated antigens PCA-1 and T10, while specific B- and T-cell determinants and EBV nuclear antigen are undetectable. In the established cell line a few cells express Ia-like and CALLA antigens. Cytogenetic analysis of MT3 cells reveals a prevalent hypertriploid karyotype with constant chromosomal aberrations consisting of 14q+, 22q- and marker chromosomes
1987
- Expression of c-myb protooncogene and other cell cycle-related genes in normal and neoplastic human colonic mucosa.
[Articolo su rivista]
Torelli, Giuseppe; Venturelli, D; Coló, A; Zanni, C; Selleri, L; Moretti, L; Calabretta, Bruno; Torelli, Umberto
abstract
The expression of c-myb, c-myc, histone H3, and ornithine decarboxylase genes was examined by Northern blot analysis in the normal and neoplastic mucosa of ten subjects affected by colon cancer. The mRNA levels of c-myb protooncogene were detected at low levels in all normal samples but were increased in the neoplastic mucosa of six cases in comparison to the normal counterpart. In five of these six cases the mRNA levels of c-myc, histone H3, and ornithine decarboxylase mRNAs were also increased, suggesting that there is a relation between the high expression of c-myb and the fraction of cycling neoplastic cells.
1987
- Immunoglobulin and T cell receptor beta chain gene rearrangements as lineage markers in human leukemias: a study of 78 cases. HAEMATOLOGICA 72, 391 397, 1987
[Articolo su rivista]
NARNI, Franco; A., Colò; D., Venturelli; L., Selleri; A., Donelli; A., Tabilio; ARTUSI, Tullio; U., Di prisco; TORELLI, Giuseppe; TORELLI, Umberto
abstract
In most cases, an excellent correlation was observed with diagnosis performed according to conventional criteria. Some cases of aberrant gene rearrangement, however, were found in acute myeloid leukemia, chronic lymphocytic leukemia and biphenotipic leukemia.
1987
- Molecular study of the Philadelphia translocation in chronic myelogenous leukemia in different stages of the disease.
[Articolo su rivista]
Torelli, Giuseppe; L., Selleri; Emilia, Giovanni; Narni, Franco; A., Colò; Zucchini, Patrizia; A., Donelli; D., Venturelli; Torelli, Umberto
abstract
The breakpoints on chromosome 22 we analyzed by molecular hybridization in 22 cases os chronic myeloid leukemia. In 3 patients the breakpoint was not detectable inside the bcr region in spite of the presence of a cytogenetically evident t(9;22) translocation. The breakpoint location remained unchanged in the 4 patients studied during after progression
1987
- Philadelphia positive chronic myeloid leukemia with 22 breakpoint outside the "beakpoint cluster region" (bcr).
[Articolo su rivista]
L., Selleri; Narni, Franco; Emilia, Giovanni; A., Colo'; Zucchini, Patrizia; D., Venturelli; A., Donelli; Torelli, Umberto; Torelli, Giuseppe
abstract
In chronic myelogenous leukemia (CML) the reciprocal translocation resulting in the Philadelphia chromosome (Ph1) leads to the formation of a chimeric transcriptional unit carrying both c-abl and bcr genetic information whose transcript is a new fused mRNA of 8.5-kilobases (kb) and whose translational product is a 210-kD phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML. Twenty patients affected by Ph1-positive CML were studied by Southern blot analysis with bcr. Unexpectedly, in three Ph1-positive patients, the breakpoint of chromosome 22 was located neither inside the bcr region nor 5' to it. Northern blot analysis of the RNAs of two of these patients showed the absence of a detectable 8.5-kb chimeric mRNA. In the third patient a chimeric mRNA was detected by a c-abl cDNA probe but failed to hybridize with a bcr cDNA probe and showed very low hybridization levels with further 5' bcr cDNA probes. The possibility is raised that in CML a breakpoint outside bcr might either still allow the formation of a chimeric mRNA, possibly through alternative splicing mechanisms, or might prevent the transcription of the chimera. In the latter case different molecular events resulting in the formation of a Ph1 chromosome may underlie the same myeloid neoplastic phenotype.
1986
- Growth-dependent expression of human Mr 53,000 tumor antigen messenger RNA in normal and neoplastic cells.
[Articolo su rivista]
Calabretta, Bruno; Kaczmarek, L; Selleri, L; Torelli, Giuseppe; Ming, Pm; Ming, Sc; Mercer, W. E.
abstract
We have investigated the expression of Mr 53,000 protein (p53) in total RNA isolated from human peripheral blood mononuclear cells stimulated by phytohemagglutinin, in serum-stimulated human diploid fibroblasts, and in normal and tumor cells of human epithelial colon tissue. We have found that the expression of p53 messenger RNA is growth regulated in human cells following kinetics similar to that previously shown in mouse 3T3 cells, and is increased in the large majority of colon adenocarcinomas in comparison to adjacent normal mucosa and adenoma. This increased expression of p53 is accompanied by a nearly proportional increase in the expression of histone H3. As the expression of histone H3 is restricted to the S phase of the cell cycle and therefore measures the growth fraction of a given population, we suggest that the increased expression of p53 observed in the large majority of colon tumors simply reflects the increased number of cycling cells frequently found in a neoplastic tissue. At variance with these findings a true overexpression of p53 was detected in one SV40-transformed human fibroblasts cell line.
1985
- Cromosomi marker ed anomalie nucleari nei linfociti di due pazienti con sindrome di Sezary/micosi fungoide. In problemi e prospettive nella medicina moderna.
[Monografia/Trattato scientifico]
Emilia, Giovanni; Torelli, Giuseppe; Sacchi, Stefano; A., Donelli; C., Fornieri; Zucchini, Patrizia; L., Selleri; Torelli, Umberto
abstract
no abstract
1985
- Study of the levels of expression of two oncogenes, c-myc and c-myb, in acute and chronic leukemias of both lymphoid and myeloid lineage..
[Articolo su rivista]
Ferrari, Sergio; Torelli, Umberto; Selleri, L; Donelli, A; Venturelli, D; Narni, Franco; Moretti, Luigi; Torelli, Giuseppe
abstract
Total cellular RNA from a series of leukemic cell populations, both myeloid and lymphoid, as well as from normal circulating lymphocytes was analysed for the expression of two cellular oncogenes, c-myc and c-myb, by Northern blot hybridization assay. Expression of c-myc but not of c-myb was observed in unstimulated normal lymphocytes. Stimulation by PHA was shown to activate the expression of both genes. Remarkably different levels of expression of c-myc were observed in ALL, whereas in CLL the expression of c-myc was uniformly low or absent. Differential expression of c-myc was detected in AML as well as in CML, c-myb was differentially expressed in AML and ALL, and absent in CLL and CML. Other single cases of hemopoietic disorders were studied, but the expression of the two oncogenes was low or absent. Neither evident genome amplification nor genome rearrangements were detected in the cell DNAs digested with restriction endonucleases.
1984
- Isolation of a cDNA clone containing a sequence complementary to the intestinal calcium-binding protein of the chick
[Articolo su rivista]
Ferrari, S.; Battini, R.; Leone, A.; Ferrari, S.; Torelli, G.; Barbiroli, B.
abstract
The present work describes the construction of a cDNA library in pBR322 plasmid from an mRNA population enriched for the intestinal calcium-binding protein (CaBP) mRNA of the chick. We report the isolation of one recombinant clone containing a vitamin D-regulated sequence, which is complementary to part of the CaBP mRNA. Northern blot hybridization experiments allowed us to identify a 1900 nucleotide RNA species as the CaBP mRNA. © 1984.
1984
- Low-dose intravenous pepsin-treated gammaglobulin for idiopathic thrombocytopenic purpura in adults.
[Articolo su rivista]
Emilia, Giovanni; Sacchi, Stefano; Torelli, Giuseppe; Selleri, L; Torelli, Umberto
abstract
no abstract
1983
- I linfomi del centro germinativo: clinica, terapia e prognosi del linfoma maligno centroblastico-centrocitico.
[Relazione in Atti di Convegno]
Mauri, C.; Federico, Massimo; Piccinini, Lino; Torelli, Giuseppe; Sacchi, Stefano; Barbieri, F.; Dini, D.; Artusi, Tullio; Silingardi, V.
abstract
Vengono riferiti i risultati di uno studio retrospettivo su 71 casi di linfoma maligno centroblastico-centrocitico osservati nei dipartimenti di Medicina interna e di Ematologia dell'Università di Modena nel periodo 1968-1979. 42 casi presentavano una architettura nodulare e 29 diffusa o nodulare-diffusa.L'età d'esordio è risultata più elevata nelle forme diffuse (52,4 anni) rispetto a quelle nodulari (44,7 anni). Nella quasi totalità dei pazienti erano presenti alla diagnosi linfoadenomegalie superficiali, in circa 1/3 localizzazioni extralinfatiche e in 27 pazienti sintomi B. L'87% dei LMcb/cc diffusi e il 63% dei nodulari già all'esordio erano in stadio III o IV.Sono riferiti i risultati delle principali indagini ematochimiche e strumentali. La terapia di induzione (mono o polichemioterapia e/o terapia radiante) ha determinato RC nel 67% delle forme nodulari e nel 37% delle forme diffuse.La sopravvivenza mediana attuariale di tutta la casistica è risultata di 91 mesi (103 mesi per le forme nodulari e 43 mesi per quelle diffuse). Al follow-up (31-12-81) dei 71 pazienti presi in esame 39 erano viventi (24 in RC e 15 in RP) e 32 deceduti (range 2-128).
1982
- Chromosomes in paroxysmal nocturnal haemoglobinuria.
[Articolo su rivista]
Emilia, Giovanni; Curci, G; Sacchi, Stefano; Bolognesi, I; Torelli, Giuseppe
abstract
no abstract
1981
- Different frequency classes of sequences in heterogeneous nuclear RNA of normal promyelocytes and lymphoblasts and of leukemic blast cells of circulating blood and of the HL60 line.
[Relazione in Atti di Convegno]
Torelli, U; Torelli, Giuseppe; Narni, Franco; Donelli, A; Ferrari, Sergio; Franchini, G; Calabretta, Bruno
abstract
No abstract available.
1981
- Presence of a highly repetitive and widely dispersed DNA sequence in the human genome.
[Articolo su rivista]
Tashima, M; Calabretta, Bruno; Torelli, Giuseppe; Scofield, M; Maizel, A; Saunders, G. F.
abstract
A genomic DNA library consisting of human DNA fragments about 18 kilobases long cloned in a bacteriophage lambda vector was found to contain a specific repeated DNA segment. The repeated sequence is present in greater than 95% of the genomic library, and selected clones contain at least two copies of the sequence. Our experiments indicate that this highly repetitive sequence (approximately 400,000 copies per haploid genome) is widely distributed in the human genome and is represented in the cytoplasmic polysomal mRNA. This sequence is homologous to the 300-base-pair Alu repeat family, the predominant repeat sequence in man.
1980
- Characteristics of macromolecular RNA metabolism in leukemic promyelocytes of the HL 60 line
[Articolo su rivista]
Torelli, Umberto; A., Donelli; G., Franchini; Calabretta, Bruno; Ferrari, Sergio; Narni, Franco; Torelli, Giuseppe; G. P., Bagnara; M. A., Brunelli
abstract
The macromolecular RNA metabolism of the HL-60 promyelocytic cell line was studied after labelling with 3H-5 uridine and sedimentation in a linear sucrose gradient. The pattern obtained in exponentially growing HL-60 cells is strictly similar to that observed in resting circulating leukemic cells, whereas cleavage of early transcripts is very rapid in HeLa cells.
1980
- Self complementary sequences in the heterogeneous nuclear RNA of leukemic cells of the HL 60 promyelocytic cell line.
[Articolo su rivista]
Torelli, Umberto; A., Donelli; G., Franchini; Ferrari, Sergio; Calabretta, Bruno; Narni, Franco; Torelli, Giuseppe; G. P., Bagnara; M. A., Brunelli
abstract
After extensive self annealing up to 30% double stranded RNA can be obtaind from HL-60 cell line. The annealing kinetics are consistent with the presence of at least two components. The smallest component is presumably transcribed from repeated DNA sequences. The largest component includes sequences annealing at low rate, as expected for sequences transcribed from unique DNA sequences..
1979
- Complete remission in a case of aplastic anemia after treatment with antilymphocyte globulin
[Articolo su rivista]
Silingardi, Vittorio; Venezia, Leonardo; Federico, Massimo; Torelli, Giuseppe; Salvo, G.
abstract
The Authors report a case of aplastic anemia, resistant to treatment with androgens and prednisone, in which bone marrow regeneration was observed after treatment with antilymphocyte globulin.This observation confirms the possibility of a immune pathogenesis in some cases of aplastic anemia, although no direct evidence was obtained supporting the existence of a humoral or cellular autoimmune process in the patient.The result obtained points to a new approach in the treatment of aplastic anemia.
1979
- Immunological evidence for the presence of double-stranded RNA regions in intact nuclei of normal human lymphocytes
[Articolo su rivista]
Torelli, Umberto; Ferrari, Sergio; Franchini, G; Donelli, A; Narni, Franco; Calabretta, Bruno; Torelli, Giuseppe
abstract
Nuclei isolated from unstimulated and PHA stimulated human lymphocytes were incubated with a labeled purified antibody to a double-stranded polyribonucleotide. A relatively high amount of double stranded RNA could be detected in intact lymphocyte nuclei.
1979
- Kinetics of hybridization to human DNA of heterogeneous nuclear RNA isolated from normal human lymphoblasts and acute leukemia blast cells.
[Articolo su rivista]
Torelli, Giuseppe; Narni, Franco; Franchini, G; Donelli, A; Ferrari, Sergio; Calabretta, Bruno; Torelli, Umberto; Bosi, Paolo
abstract
Heterogeneous nuclear RNA was extracted from normal PHA-stimulated human lymphocytes and acute myeloid leukemia blast cells. Experiments were performed to determine the hybridization kinetics of these RNA's to human DNA. The best least squares solutions indicate in the hybridization reaction of both normal and leukemic RNA two main components. For leukemic cell RNA the rate constants of both components were significantly different from that of normal cell RNA. In particular, the difference between the rate constants of the second lower component suggests that the slowly hybridizing sequences in leukemic cell RNA have a degree of repetition higher than of the corresponding sequences of normal cell RNA.
1979
- Reassociation kinetics of the DNA of human acute leukemia cells.
[Articolo su rivista]
Torelli, Giuseppe; Cadossi, Ruggero; Ferrari, Sergio; Narni, Franco; Ferrari, Stefano; Montagnani, Giuliano; Torelli, Umberto; Bosi, Paolo
abstract
Human DNA isolated from normal phytohaemagglutinin-stimulated human lymphocytes and from acute leukemia blast cells have been studied by renaturation techniques using hydroxyapatite binding and DNA hyperchromism. In the leukemic genome, the unique sequences account for 62% of the genome of leukemic DNA. Repetitive sequences may be subdivided into at least three fractions: (a) foldback sequences, which represent 5% of the genome; (b) sequences with high repetition frequency (3. 10(4) times on the average), which represent 12% of the genome; (c) sequences with low repetition frequency (10 times on the average), which represent 16% of the genome. The average length of the repetitive sequences is evaluated to be between 200 and 500 nucleotides. There are at least two patterns of interspersion of repetitive sequences with unique sequences of different length: short (about 2000 nucleotides on average) and long (not defined). The results of our experiments on DNA from normal phytohaemagglutinin-stimulated human lymphocytes are in close agreement with those reported by other authors studying different types of human cells. The human leukemic DNA, as far as the parameters that have been studied, does not significantly differ from normal human DNA.
1979
- Sindrome mediastinica da mieloblastoma quale manifestazione d'esordio di leucemia mieloide acuta
[Articolo su rivista]
Silingardi, Vittorio; Artusi, Tullio; Torelli, Giuseppe; Federico, Massimo
abstract
The authors report a case of acute myeloblastic leukemia which at the onset was characterized by a granuloblastic mediastinal tumor, without the appearance of a blastic population in the peripheral blood. The diagnosis was allowed by the cytological and cytochemical study of the pleural effusion. The autopsy confirmed the invasion of several organs by the myeloid malignant cells.The authors describe the clinical and histopathological characteristics of the disease. They point out that the histogenesis of this case and other similar ones reported in the literature remains obscure. The possibility is suggested that microenvironmental factors may have a critical role in facilitating the in situ proliferation of circulating blast cells with formation of solid tumor masses.
1979
- Studio clinico immunologico di sei casi di morbo di Behcet
[Articolo su rivista]
Silingardi, Vittorio; Montemurno, C.; Venezia, Leonardo; Franceschi, C.; Riva, P. C.; Emilia, Giovanni; Masi, M.; Merelli, E.; Torelli, Giuseppe; Licastro, F.; Fantini, M. P.; Federico, Massimo
abstract
Vengono riferiti 6 casi di morbo di behcet, la cui diagnosi è risultata particolarmente ardua, poichè la triade sintomatologica propria della malattia (afte orali, ulcere genitali, uveite) era mascherata dai disturbi secondari alla localizzazione del processo morboso ad altri organi ed apparati.Le indagini immunologiche eseguite hanno confermato la presenza in questi pazienti di alterazioni di vari tests in vivo ed in vitro ed in particolare sono state evidenziate iper-reattività cutanea aspecifica in 5 casi ed esaltata blastizzazione linfocitaria spontanea e dopo PHA.In base all'esito delle indagini eseguite ed ai dati della letteratura viene prospettata la possibilità che nel morbo di Behcet coesistano alterazioni immunologiche e dei meccanismi che relgolano l'attivazione delle chinine, del complemento e della coagulazione.Da un punto di vista terapeutico è stata confermata l'efficacia, almeno temporanea, della terapia corticosteroidea ed è stata sperimentata per la prima volta in questi pazienti la globulina antilinfocitica, che potrebbe sostituire gli antiblastici immunodepressori già usati con risultati soddisfacenti nei portatori di morbo di Behcet.
1978
- The primary product of DNA transcription in the blast cell of acute leukemia. Its characterization as an approach to the understanding of the origin of the blast crisis of chronic myeloid leukemia
[Articolo su rivista]
Torelli, Umberto; Torelli, Giuseppe; Cadossi, Ruggero; Ferrari, Stefano; Ferrari, Sergio; Montagna, G; Narni, Franco; Franchini, G; Donelli, A.
abstract
The primary product of transcription, the heterogeneous nuclear RNA, is processed at a very low rate in leukemic blast cells. The proportion of double-helical segments, presumably the recognition sites of cleaving enzymes, is much greater. An alteration of the mechanisms dictating the formation of secondary structure in heterogeneous nuclear RNA might cause the inhibition of genome expression in leukemic cells.
1977
- Immunological assay of double-helical segments in RNA fractions of different molecular size extracted from acute myeloid leukemia blast cells.
[Articolo su rivista]
Torelli, Umberto; Ferrari, Sergio; Montagnani, Giuliano; Torelli, Giuseppe; Cadossi, Ruggero; Ferrari, Stefano; Narni, Franco
abstract
Whole-cell RNA, extracted from acute myeloid leukemia blast cells, was fractionated by sedimentation through sucrose gradients. The proportion of double-helical segments present in each fraction was then determined by a quantitative microcomplement fixation assay that specifically measures double-helical RNA. Sizable amounts of double-helical segments were detected in all fractions of cellular RNA corresponding to S values higher than approximately 20. In all cell populations examined the highest proportion of double-helical segments was found in RNA fractions sedimenting faster then the 45 S ribosomal precursors RNA, i.e., in fractions including only heterogeneous nuclear RNA.
1977
- In vitrocleavage of 45S pre-ribosomal RNA and of giant heterogeneous RNA extracted from human leukemic cells.
[Articolo su rivista]
Torelli, Umberto; Ferrari, Sergio; Torelli, Giuseppe; Cadossi, Ruggero; Ferrari, Stefano; Montagnani, Giuliano; Narni, Franco
abstract
45S ribosomal precursor RNA and large heterogeneous RNA molecules (greater than 45S) extracted from human leukemic cells were incubated in vitro with purified RNase III, which specifically attacks double-helical RNA regions. About 50% of the ribosomal precursor was cleaved into two major fragments sedimenting at 28S and 32S respectively. A limited number of cleavages was also introduced in about 40% of heterogeneous RNA molecules sedimenting faster than 45S, causing a partial 'shift' to a polydisperse distribution in the 10S-45S range
1977
- Trapianto di midollo osseo nelle aplasie midollari.
[Articolo su rivista]
Silingardi, Vittorio; Torelli, Giuseppe; Dagna Bricarelli, F.; Secchi, E.; Ferrari, S.; Montagnani, G.; Curci, G.; Federico, Massimo; Emilia, Giovanni; DI PRISCO, Alfredo Ubaldo; Venezia, Leonardo; Misley, A.; Torelli, Umberto; Mauri, C.
abstract
Dopo un breve cenno sulla etico-patogenesi delle aplasie midollari, gli AA. riferiscono i dati più salienti della letteratura sul trapianto di midolo osseo allogenico ed isogenico in tali emopatie.Vengono riferiti i risultati a distanza osservati dagli AA. nel primo caso di aplasia midollare globale trattato in Italia con mielotrapianto isogenico.Gli AA. schematizzano infine le indicazioni al mielotrapianto nelle aplasie midollari, senza minimizzare i pericoli che tuttora comporta tale trattamento e gli insuccessi cui si può incorrere.
1976
- Accumulation of giant heterogeneous RNA molecules in acute myeloid leukemia blast cells.
[Articolo su rivista]
Torelli, Umberto; Torelli, Giuseppe; Cadossi, Ruggero; Ferrari, Stefano; Ferrari, Sergio; Narni, Franco; Montagnani, Giuliano
abstract
Time course and "chase" experiments showed that, after incubation of acute myeloid leukemia blast cells with a labeled RNA precursor, a large proportion of radioactivity remained associated with RNA molecules larger than 45 S even after several hr. Double-labeling experiments with [5-3H]uridine and [methyl-14C]methionine indicated that unmethylated giant heterogeneous RNA larger than 45 S is processed much more slowly than the 45 S ribosomal precursor, so that relatively large amounts of fairly stable RNA of the former class accumulate in the cell. The measurement of labeled giant heterogeneous RNA molecules bound to polyuridylate-fiberglass filters showed that molecules carrying polyadenylate segments seemingly turn over faster than those lacking polyadenylate.