Mario Tiribelli

Publications (70) View all

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  Available from: Mario Tiribelli

  Article: Impact of BCR-ABL mutations on response to dasatinib after imatinib failure in elderly patients with chronic-phase chronic myeloid leukemia.

  Mario Tiribelli, Roberto Latagliata, Luigiana Luciano, Fausto Castagnetti, Antonella Gozzini, Giovanna Rege Cambrin, Mario Annunziata, Fabio Stagno, Patrizia Pregno, Francesco Albano, Elisabetta Abruzzese, Pellegrino Musto, Enrico Montefusco, Carmen Fava, Renato Fanin, Fabrizio Pane, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Paolo Vigneri
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  ABSTRACT: To assess the impact of BCR-ABL kinase domain mutations on dasatinib response in elderly chronic myeloid leukemia (CML) patients, we analyzed the outcome of 76 individuals aged >60 affected by imatinib-resistant chronic-phase CML. We found that 36 cases (47 %) displayed mutations before dasatinib. Compared to non-mutated patients, subjects with point mutations had a worse response to dasatinib, with significantly lower rates of complete cytogenetic response (57 vs 32 %), higher percentage of primary resistance (16/36 vs 6/40) and a trend towards a shorter median event-free survival. Our data suggest that, in elderly patients, detection of BCR-ABL mutations negatively affects response to dasatinib.
  Annals of Hematology 10/2012; · 2.62 Impact Factor
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  Available from: Marzia Salvucci

  Article: Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study.

  F Efficace, M Baccarani, G Rosti, F Cottone, F Castagnetti, M Breccia, G Alimena, A Iurlo, A R Rossi, S Pardini, F Gherlinzoni, M Salvucci, M Tiribelli, M Vignetti, F Mandelli
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  ABSTRACT: Background:Optimal adherence to imatinib therapy is of paramount importance to maximise treatment effectiveness in patients with chronic myeloid leukaemia (CML). The main objective of this study was to investigate patient-reported personal factors associated with adherence behaviour.Methods:Analysis was conducted on 413 CML patients receiving long-term therapy with imatinib. Adherence behaviour was measured with the Morisky Medication Adherence Scale and personal factors investigated included: quality of life, perceived social support, fatigue, symptom burden, psychological wellbeing and desire for additional information. Key socio-demographic and treatment-related factors were also taken into account. Univariate and multivariate logistic regression analyses were used to investigate factors associated with optimal adherence to therapy.Results:In all, 53% of patients reported an optimal adherence behaviour. The final multivariate model retained the following variables as independent predictors of optimal adherence to therapy: desire for more information (ref. no), odds ratio (OR)=0.43 (95% confidence interval (CI), 0.29-0.66; P<0.001), social support (higher score representing greater support), OR=1.29 (95% CI, 1.11-1.49; P<0.001) and concomitant drug burden (ref. no), OR=1.82 (95% CI, 1.18-2.80; P=0.006).Conclusion:This study suggests that a higher level of social support, satisfaction with information received and concomitant drug burden are the main factors associated with greater adherence to long-term imatinib therapy.
  British Journal of Cancer 08/2012; 107(6):904-9. · 5.04 Impact Factor
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  Available from: Marzia Salvucci

  Article: Evaluation of residual CD34(+) Ph(+) progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first-line nilotinib therapy.

  Marzia Defina, Micaela Ippoliti, Alessandro Gozzetti, Elisabetta Abruzzese, Fausto Castagnetti, Rosaria Crupi, Mario Tiribelli, Massimo Breccia, Marzia Salvucci, Lara Aprile, Claudia Baratè, Antonella Gozzini, Gianantonio Rosti, Francesco Lauria, Monica Bocchia
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  ABSTRACT: Compared with imatinib, nilotinib is a potent breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene (bcr-abl) kinase inhibitor, and it induces higher rate and rapid complete cytogenetic response (CCyR), yet no clinical data are available regarding its efficacy against chronic myeloid leukemia (CML) stem cells. Earlier studies demonstrated that clusters of differentiation 34-positive, Philadelphia chromosome-positive (CD34(+) Ph(+) ) cells are detectable in about 45% of patients with CML, despite being on long-term imatinib therapy and having achieved sustained CCyR. CD34(+) cells from bone marrow of de novo CML patients in the chronic phase (n = 24) treated with nilotinib (median duration of therapy, 22 months) were isolated and scored for BCR-ABL by fluorescent in situ hybridization (FISH) analysis. Similar analysis was also performed in 5 de novo CML chronic phase patients who achieved CCyR within 3 months of nilotinib therapy. FISH evaluation of a median of 100 CD34(+) nuclei per patient revealed that only 1 of 20 (5%) evaluable patients showed residual Ph(+) progenitor cells. In this patient, just 1 of 140 (0.7%) CD34(+) interphase nuclei was found to be positive for BCR-ABL. Surprisingly, no CD34(+) Ph(+) cells were found even in those 5 patients evaluated after 3 months of nilotinib treatment. This study assessed for the first time the persistence of CD34(+) Ph(+) cells during nilotinib first-line treatment. Preliminary results showed that in patients in CCyR, even after short-term nilotinib therapy, residual leukemic progenitors are very rarely detected compared with imatinib-treated CCyR patients. It is yet to be determined if these findings will have an impact in the path to a cure of CML with tyrosine kinase inhibitors. Cancer 2012. © 2012 American Cancer Society.
  Cancer 04/2012; 118(21):5265-9. · 4.77 Impact Factor
• Article: Histone post-translational modifications associated to BAALC expression in leukemic cells.

  Alessandra Franzoni, Nadia Passon, Dora Fabbro, Mario Tiribelli, Daniela Damiani, Giuseppe Damante
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  ABSTRACT: BAALC expression is an indicator of aggressiveness in acute myelogenous leukemia (AML). Overexpression of this gene is associated to poor of clinical outcome. It is known that post-translational histone modifications control gene transcription. Thus, here we have investigated BAALC expression and post-translational histone modifications in leukemia cell lines. We show that Kasumi-6 and Kyo cells have high and low BAALC mRNA levels, respectively. Moreover, we demonstrate that these cell lines present distinct profiles in terms of histone post-translational modifications (H3K9K14 acetylation, H3K4 trimethylation and H3K23 trimethylation) at the level of BAALC promoter. These findings, in light of recent data on how histone post-translational modifications control gene expression, indicate that BAALC gene is "paused" and that in leukemia cells its transcription can be activated or repressed by mechanisms acting on epigenetic marks.
  Biochemical and Biophysical Research Communications 12/2011; 417(2):721-5. · 2.48 Impact Factor
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  Available from: Mario Tiribelli

  Article: Nutlin-3 downregulates the expression of the oncogene TCL1 in primary B chronic lymphocytic leukemic cells.

  Rebecca Voltan, Maria Grazia di Iasio, Raffaella Bosco, Nicola Valeri, Yuri Pekarski, Mario Tiribelli, Paola Secchiero, Giorgio Zauli
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  ABSTRACT: The oncogene TCL1 plays a key role in the development of B chronic lymphocytic leukemia (B-CLL), but it is not known whether TCL1 could be modulated by therapeutic approaches. B-CLL patient samples (n = 35) and B leukemic cell lines (EHEB, JVM2, JVM3, MEC1, MEC2, and BJAB) with different p53 status were exposed to Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction. Modulations of the steady-state mRNA levels of TCL1 were analyzed by quantitative real-time PCR and Western blotting in both primary B-CLL samples and leukemic cell lines. In addition, transfection experiments with either p53 siRNA or with a TCL1 expression plasmid were carried out in the EHEB B-CLL cell line. Upon ex vivo treatment with Nutlin-3, TCL1 was significantly (P < 0.05) decreased in 23 of 28 B-CLL p53(wild-type). The functionality of the p53 pathway in the same leukemic cell samples was underscored by the concomitant ability of Nutlin-3 to significantly (P < 0.05) upregulate the p53 target gene MDM2 in the p53(wild-type) leukemic cells. The dependence of TCL1 downregulation by a functional p53 pathway was confirmed in a panel of B lymphoblastoid cell lines and by p53 knockdown experiments with p53 siRNA. The importance of TCL1 in promoting leukemic cell survival was underscored in transfection experiments, in which TCL1 overexpression significantly counteracted the Nutlin-3-mediated induction of apoptosis in EHEB. Our data indicate that the Nutlin-3 downregulates TCL1 mRNA and protein, which likely represents an important molecular determinant in the proapoptotic activity of Nutlin-3.
  Clinical Cancer Research 08/2011; 17(17):5649-55. · 7.74 Impact Factor