Murine double minute-2 expression in B-cell chronic lymphocytic leukemia: correlation with apoptosis and disease outcome

Abstract

Introduction B-cell chronic lymphocytic leukemia (B-CLL) is characterized by accumulation of quiescent monoclonal CD5+ B cells, which arise from undefined defects in apoptotic cell death. murine double minute-2 (MDM2) oncoprotein exists in an autoregulatory feedback loop with the tumor suppressor protein p53 and block p53-mediated transactivation and apoptosis. Aim of this work The aim of the study was to evaluate the overexpression of MDM2 in B-CLL patients and correlate it with apoptosis using annexin-V expression and disease outcome. Patients and methods This study was conducted on 55 patients including 45 patients with typical B-CLL; their ages ranged from 55 to 72 years, with a mean age of 58.55 ± 3.9 years. Ten age-matched and sex-matched apparently healthy individuals were included as the control group. The diagnosis of B-CLL was based on clinical, hematological, immunophenotypic, and cytogenetic criteria. Annexin-V and MDM2 oncoprotein expression was assessed by flow cytometric analysis. Results Our study revealed that MDM2 was overexpressed in 53% of B-CLL cases and it was significantly elevated in comparison with the control group (P < 0.001). There was an inverse correlation between MDM2 overexpression and apoptosis (P < 0.001). The mean level of MDM2 expression was significantly reduced after therapy compared with the pretreatment level in the responder group (P < 0.001), whereas there was no significant difference (P>0.05) in the nonresponder group. The expression of MDM2 significantly correlated with the percentage of CD38 expression, LDH level, and B2M level (P < 0.001, P < 0.001, and P < 0.001, respectively) and patients who had responded to treatment showed a significant increase in the level of annexin-V (P < 0.001). MDM2 expression, percentage of CD38 expression, and LDH and B2M levels were significantly higher in the high-risk patients compared with low-risk and intermediate-risk patients (P < 0.001, P < 0.01, P < 0.05, and P < 0.001, respectively).Conclusion MDM2 expression was inversely correlated with apoptosis, with decreased MDM2 expression in responder patients.