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

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.