TP53 is a tumor suppressor gene frequently mutated in human cancers and is generally associated with poor outcomes. TP53 mutations are found in approximately 5% to 10% of patients with de novo acute myeloid leukemia (AML), more frequently observed in elderly patients and those with therapy-related AML. Despite recent advances in molecular profiling and the emergence of targeted therapies, TP53-mutated AML remains a challenge to treat. Current treatment strategies, including conventional chemotherapy, hypomethylating agents, and venetoclax-based therapies, have shown limited efficacy in TP53-mutated AML, with low response rates and poor overall survival. Allogeneic hematopoietic stem cell transplantation is a potentially curative option; however, its efficacy in TP53-mutated AML depends on comorbid conditions and disease status at transplantation. Novel therapeutic modalities, including immune-based therapies, did show promise in early-phase studies but did not translate into effective therapies in randomized controlled trials. This review provides a comprehensive overview of TP53 mutations in AML, outcomes based on allelic burden, clinical implications, and therapeutic challenges.

TP53 是一种在人类癌症中经常发生突变的抑癌基因，通常与不良预后相关。TP53 突变见于大约 5%-10% 的新发急性髓系白血病 （AML） 患者，更常见于老年患者和治疗相关 AML 患者。尽管最近在分子分析方面取得了进展，并且出现了靶向治疗，但 TP53 突变的 AML 仍然是一个难以治疗的挑战。目前的治疗策略，包括常规化疗、低甲基化药物和基于维奈克拉的疗法，对 TP53 突变的 AML 疗效有限，反应率低，总生存期差。同种异体造血干细胞移植是一种潜在的治愈选择;然而，其对 TP53 突变 AML 的疗效取决于移植时的合并症和疾病状态。新的治疗方式，包括基于免疫的疗法，确实在早期研究中显示出前景，但在随机对照试验中并未转化为有效的疗法。本综述全面概述了 AML 中 TP53 突变、基于等位基因负荷的结局、临床意义和治疗挑战。