Frequency and prognostic significance of murine double minute protein-2 overexpression and p53 gene mutations in childhood acute lymphoblastic leukemia

Abstract

Aim: Determination of frequency and prognostic significance of murine double minute protein-2 (MDM-2) over expression and its association with p53 status in children with acute lymphoblastic leukemia (ALL).

Methods: MDM-2 expression by flow cytometry and p53 gene status by PCR were determined in peripheral blood or bone marrow of 46 ALL children (at initial diagnosis) and control group.

Results: MDM-2 was significantly overexpressed in 15 patients (32·6%). p53 mutation was detected in six out of 46 patients at initial diagnosis, three of them were out of 29 cases achieving complete remission (CR) and the other three cases were out of 17 of relapsed patients, which is significantly higher than CR group (P<0·05). Positive correlation was found between the MDM-2 overexpression and initial WBCs count, peripheral blast cell count and presence of CNS blasts (P<0·05, <0·05 and <0·05 respectively).

Conclusion: MDM-2 is overexpressed in a significant number of childhood ALL, and more often observed in the poor outcome group and its frequency is not related to p53 status. Measurement of MDM-2 as a bad prognostic marker even in cases with non-mutant p53 is very important. Moreover, MDM-2 may be a potential molecular target for production of new cancer therapy.

Keywords:

• MDM-2 OVER EXPRESSION
• P53 MUTATIONS
• PROGNOSIS
• CHILDHOOD LEUKEMIA