Shahzad Moazzam, Amin Muhammad Kashif, Daver Naval G, Shah Mithun Vinod, Hiwase Devendra, Arber Daniel A, Kharfan-Dabaja Mohamed A, Badar Talha
Division of Hematology and Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Division of Hematologic Malignancies & Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS, USA.
Blood Cancer J. 2024 Nov 19;14(1):202. doi: 10.1038/s41408-024-01186-5.
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肿瘤抑制基因，通常与不良预后相关。在约5%至10%的初发急性髓系白血病（AML）患者中可发现TP53突变，在老年患者和治疗相关AML患者中更常见。尽管最近在分子谱分析方面取得了进展，且出现了靶向治疗，但TP53突变的AML治疗仍然是一项挑战。目前的治疗策略，包括传统化疗、去甲基化药物和基于维奈托克的疗法，在TP53突变的AML中疗效有限，缓解率低且总生存期不佳。异基因造血干细胞移植是一种潜在的治愈选择；然而，其在TP53突变AML中的疗效取决于移植时的合并症和疾病状态。包括免疫疗法在内的新型治疗方式在早期研究中确实显示出前景，但在随机对照试验中并未转化为有效的治疗方法。本综述全面概述了AML中的TP53突变、基于等位基因负担的预后、临床意义和治疗挑战。
