Overexpression of the MDM2 oncogene in leukemia and lymphoma.
A cellular phosphoprotein that binds to and inactivates p53 has recently been identified as a product of the oncogene MDM2. Amplification of the MDM2 gene was found in more than a third of sarcomas and in a subset of malignant gliomas. Despite the absence of amplification, the MDM2 gene was overexpressed in some types of leukemias and lymphomas. Overexpression was significantly more frequent in the low-grade type of B-cell non-Hodgkin's lymphoma (B-NHL) than in the intermediate/high grade types of lymphoma and the overexpression was also significantly more frequent in the advanced rather than the earlier stages of B-cell chronic lymphocytic leukemia (B-CLL) and B-NHL. This suggests that MDM2 could play a role, via the p53 pathway, in tumorigenicity and/or in disease progression in some hematological malignancies. However, in the light of our findings that, in a few cases, both the overexpression of MDM2 and mutant-type p53 was seen, it is possible that MDM2 overexpression may also promote neoplastic growth by mechanisms other than inactivation of the p53 protein.
Watanabe
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Ichikawa
A
A
Saito
H
H
Hotta
T
T
D000818:Animals; D005784:Gene Amplification; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2