Decoding the molecular drivers of TP53 ‐mutant acute myeloid leukaemia: Clinical implications and prognostic insights

Summary This study aimed to investigate the distinct clinical characteristics and molecular features of TP53 ‐mutant acute myeloid leukaemia (AML) patients. We retrospectively analysed 193 TP53 ‐mutant AML patients. Better responses were observed in patients treated with the venetoclax in combination with hypomethylating agent (VEN + HMA) regimen compared to those receiving the ‘ 3 + 7 ’ regimens (composite complete remission [CRc], 53.8% vs. 30.2%; p = 0.018). TP53 V272 mutation was associated with a lower relapse rate (0% vs. 35.2%; p = 0.041). The single hit group exhibited superior OS compared to the multi‐hit group (the median overall survival [OS]: 14.3 months vs. 10.8 months; p = 0.029). TP53 ‐mutant AML patients with CEBPA bZIP in‐frame mutations showed prolonged OS (the median OS: 25.2 months vs. 13.8 months; p = 0.036). Better prognoses were also shown in patients with RUNX1‐RUNX1T1 fusion gene (the median OS: 31.1 months vs. 13.7 months; p = 0.002). Multivariate analysis identified three significant prognostic factors for OS: RUNX1‐RUNX1T1 fusion gene (hazard ratio [HR] = 0.23, 95% confidence interval [CI], 0.08–0.63; p = 0.005), RUNX1 mutation (HR = 1.84; 95% CI, 1.14–2.96; p = 0.012) and FLT3‐ITD mutation (HR = 3.14; 95% CI, 1.80–5.47; p = 0.001). In conclusion, molecular factors matter in influencing the prognosis of TP53 ‐mutant AML patients. Among them, TP53 mutation sites merit particular attention.