EXPRESSION PROFILE OF MDM-2 PROTEINS IN CHRONIC LYMPHOCYTIC-LEUKEMIA AND THEIR CLINICAL RELEVANCE

The MDM-2 oncoprotein exists in an autoregulatory feedback loop with t he tumor suppressor protein p53. Therefore, intracellular levels of th ese two proteins may play important roles in cell proliferation and tu morigenesis. Several MDM-2 proteins (Mr 35-100 Kd) have been demonstra ted in human cell lines. We report here the expression profile of MDM- 2 and p53 proteins in 87 cases of chronic lymphocytic leukemia (CLL) a s detected by immunoblot analysis. The MDM-2 proteins (p57, p59, p67, and p90) were found to be overexpressed in different combinations in 5 6/87 (64%) of cases of CLL when compared with normal volunteers. The M DM-2 protein p57 was predominantly overexpressed 46/87 (53%) in CLL. I n 22/87 (25%) cases of CLL p57 was overexpressed alone, and in 24/87 ( 28%) cases it was co-overexpressed with other MDM-2 proteins p59/p67/p 90. Six of the 87 cases of CLL showed overexpression of the tumor supp ressor protein p53 by immunoblot analysis, and five of those cases als o co-overexpress MDM-2 protein p57. No statistically significant corre lation of MDM-2 protein overexpression to clinical disease stage and h istory of previous chemotherapy of CLL patients has been found. Howeve r, considering the oncogenic potential of overexpressed MDM-2 proteins , a possible role of MDM-2 proteins in the promotion of CLL disease re mains to be evaluated. (C) 1997 Wiley-Liss, Inc.