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The human MDM-2 oncogene is overexpressed in leukemias
CE Bueso-Ramos, Y Yang, E deLeon, P McCown, SA Stass and M Albitar
Hematopathology Program, University of Texas M.D. Anderson Cancer Center,
Houston 77030-4095.
The human homologue of the mouse double minute 2 (MDM-2) gene codes for a
cellular protein that forms a complex with the mutant and wild-type p53
protein and modulates its trans-activation activity. Overexpression of the
MDM-2 gene in cells increases their tumorigenic potential and overcomes the
growth-suppressive activity of p53. Previous reports have shown that the
MDM-2 gene is amplified in approximately one third of human sarcomas. To
examine the role of MDM-2 in leukemia, we analyzed MDM-2 gene amplification
and mRNA expression in various types of leukemias. We did not detect gene
amplification in any of the 48 cases of leukemia that we examined. In
contrast, we observed significant MDM- 2 mRNA overexpression in 34 of 64
cases (53%). The level of mRNA overexpression in some cases of leukemias
was comparable to that observed in some cases of sarcomas, which
demonstrate more than 50-fold MDM-2 gene amplification. Furthermore, we
divided these cases into different prognostic groups according to their
karyotypic abnormalities. MDM-2 overexpression seemed to be associated with
unfavorable chromosomal abnormalities. These findings suggest that the
expression of the MDM-2 gene is altered in a significant fraction of human
leukemias and MDM-2 may play a significant role in leukemogenesis. In
addition, these results suggest that mechanisms other than gene
amplification may play a significant role in deregulating the MDM-2
expression.
Volume 82,
Issue 9,
pp. 2617-2623,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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