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频繁发生突变的肿瘤抑制基因，通常与不良预后相关。在初诊急性髓系白血病（AML）患者中，约有5%至10%可检测到TP53突变，这一比例在老年患者和治疗相关AML中更为常见。尽管分子谱分析技术近期取得进展且靶向治疗不断涌现，TP53突变的AML仍是治疗难题。当前治疗策略包括传统化疗、低甲基化剂以及基于维奈托克的疗法，但对TP53突变AML疗效有限，表现为缓解率低且总生存期较差。异基因造血干细胞移植是潜在治愈手段，但其疗效取决于移植时的合并症及疾病状态。新型治疗模式（包括免疫疗法）在早期研究中展现希望，但在随机对照试验中未能转化为有效疗法。本综述全面阐述AML中TP53突变的特点、等位基因负荷对预后的影响、临床意义及治疗挑战。
What have we learned about TP53-mutated acute myeloid leukemia?
肿瘤(癌症)患者之家