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Prognostic value of p53 gene mutations and the product expression in de novo acute myeloid leukemia
Author(s) -
Nakano Yasuyuki,
Naoe Tomoki,
Kiyoi Hitoshi,
Kitamura Kunio,
Minami Saburo,
Miyawaki Shuichi,
Asou Norio,
Kuriyama Kazutaka,
Kusumoto Shuya,
Shimazaki Chihiro,
Akiyama Hideki,
Saito Kenji,
Nishimura Miki,
Motoji Toshiko,
Shinagawa Katsuji,
Saito Hidehiko,
Ohno Ryuzo
Publication year - 2000
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1034/j.1600-0609.2000.90138.x
Subject(s) - missense mutation , mutation , myeloid leukemia , biology , cancer research , leukemia , gene mutation , gene , microbiology and biotechnology , medicine , genetics
In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. However, the prognostic significance of the accumulation remains unknown in AML. 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 patients with de novo AML. The p53 mutation detectable (mutation + ) group had a worse prognosis ( p =0.0009) than the mutation not detectable (mutation − ) group. Multivariate analysis showed that the p53 mutation was an independent 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‐p53 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 according to the accumulation, because the mutation − /accumulation + group ( N =8) tended to have a good prognosis. These findings indicate that molecular detection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presumably due to upstream signals of p53.