MULTIPLE PATTERNS OF MDM-2 DEREGULATION IN HUMAN LEUKEMIAS - IMPLICATIONS IN LEUKEMOGENESIS AND PROGNOSIS

被引：40

作者：

BUESORAMOS, CE ^{[1
]}

MANSHOURI, T ^{[1
]}

HAIDAR, MA ^{[1
]}

HUH, YO ^{[1
]}

KEATING, MJ ^{[1
]}

ALBITAR, M ^{[1
]}

机构：

[1] UNIV TEXAS,MD ANDERSON CANCER CTR,DIV LAB MED,HEMATOPATHOL PROGRAM,HOUSTON,TX 77030

来源：

LEUKEMIA & LYMPHOMA | 1995年 / 17卷 / 1-2期

关键词：

MDM-2; ISOFORMS; LEUKEMIA; GENE DEREGULATION; RT-PCR;

D O I：

10.3109/10428199509051698

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The human analogue of the mouse double minute-2 (MDM-2) protein binds to p53 protein and abrogates its tumor-suppressing activity. MDM-2 overexpression may represent an alternative mechanism to p53 mutation for escaping the p53-mediated growth control. Interestingly, multiple MDM-2 protein isoforms have been described and the possibility of functional differences between various isoforms has been raised. Previously, we demonstrated significant MDM-2 mRNA overexpression in human leukemias and suggested that MDM-2 overexpression may be a marker of aggressiveness of the disease. Polyclonal antibodies (Ab) have been generated to detect various isoforms of the MDM-2 protein. Using these Abs, we confirmed MDM-2 protein overexpression in leukemias. Furthermore, we observed heterogeneity in the isoforms expressed in various types of leukemias. In addition, we demonstrated that analysis by flow cytometry could be used as a diagnostic tool for detecting altered MDM-2 protein expression in leukemias. Here we review and expand our initial observations and confirm MDM-2 mRNA and protein overexpression by reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and western blot analyses. Understanding the possible role of MDM-2 oncogene expression in leukemias may establish the scientific basis for new therapeutic approaches.

引用

页码：13 / 18

页数：6

共 35 条

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