mdm2-P2 transcript levels predict the functional activity of the p53 tumor suppressor in primary leukemic cells

Abstract

The mdm2-P2 promoter is a transcriptional target of the p53 tumor suppressor. The aim of this study was to determine if there is an association between the level of these transcripts and the status of the p53 gene in human leukemic cells. A correlation between mdm2-P2 transcript levels and p53 gene status was observed in all cell lines examined. Primary malignant cells from 10 leukemic patients were also analysed for both mdm2-P2 levels and p53 gene status. All five patients with detectable mdm2-P2 transcripts possessed wild-type p53 alleles. However, only two of five patients with undetectable mdm2-P2 transcripts possessed mutant p53. mdm2-P2 levels were also determined in primary leukemic cells from 14 additional cases both before and after in vitro exposure to cisplatin. The p53 gene was found to be wild-type in all cases where mdm2-P2 levels were induced by cisplatin. There were four cases where no, or only modest, increases in mdm2-P2 levels were detected after cisplatin exposure. Two of these patients were found to harbor mutant p53 while one other possessed leukemic cells with elevated levels of mdm2 protein. These results show that induction of mdm2-P2 transcripts can be used to predict the presence of transcriptionally active p53 in primary leukemic cells.