Prognostic value of p53 gene mutations and the product expression in de novo acute myeloid leukemia

In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent bu t associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. How ever, the prognostic significance of the accumulation remains unknown in AM L. In this study, we compared the prognostic value of p53 mutations versus accumulation of the product. p53 mutations were found in 9 (4.5%) of 200 pa tients with de novo AML. The p53 mutation detectable (mutation(+)) group ha d a worse prognosis (p=0.0009) than the mutation not detectable (mutation(- )) group. Multivariate analysis showed that the p53 mutation was an indepen dent factor (p=0.005) for short overall survival as well as 60 yr or older (p=0.001) and unfavorable karyotypes (p=0.001). In 79 of the 200 patients, the expression of p53 was studied by immunocytochemistry (ICC) using anti-p 53 monoclonal antibody (DO-7). All samples carrying missense mutations (N=6 ) were positive for ICC in over 15% of nuclei of each sample, chosen as the optimized cutoff value of p53 accumulation. Accumulation was thus found in 14 of the 79 patients. However, there was no prognostic difference accordi ng to the accumulation, because the mutation (-)/accumulation(+) group (N=8 ) tended to have a good prognosis. These findings indicate that molecular d etection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presuma bly due to upstream signals of p53.