Clinical significance of TP53 mutations in patients with acute myeloid leukemia: the HM-SCREEN-JAPAN 01/02 study

Mutant TP53 (mTP53) variants are diverse, and residual wild-type p53 function (functional, non-functional), gain-of-function (GOF) mTP53, and the number of mTP53 (single-hit, multi-hit) can affect prognosis. We used next-generation sequencing to evaluate the association between qualitative and quantitative mTP53 abnormalities and overall survival (OS) in 330 patients with acute myeloid leukemia (AML) enrolled in the Japanese multicenter study HM-SCREEN-JAPAN 01/02. Patients with single- and multi-hit mTP53 had a worse prognosis than patients with wild-type TP53 (median OS: 16.1 months vs. 7.5 months vs. 41.6 months). Patients with multi-hit mTP53 had a worse prognosis (P = 0.011). Patients with both mTP53 and complex karyotype (CK) had a worse prognosis than patients with either mTP53 or CK (median OS: 7.6 months vs. 15.0 months vs. 18.9 months; P = 0.03). Residual function did not affect prognosis in patients with single-hit mTP53 (median OS: 24.9 months vs. 16.1 months; P = 0.985), and prognosis did not differ between patients with GOF mTP53 and those with non-GOF mTP53 (median OS: 9.5 months vs. 9.8 months; P = 0.913). Quantitative abnormalities in the TP53 gene affected prognosis, suggesting that qualitative abnormalities did not.