急性髓系白血病 (AML) 是一种造血干细胞的侵袭性恶性肿瘤，其特征是细胞分化受阻、增殖失控和细胞扩张，损害健康的造血功能，导致全血细胞减少和易受感染。多种遗传和染色体畸变在 AML 中发挥作用并影响患者的治疗结果。 TP53是一个关键的肿瘤抑制基因，参与多种细胞特征，如细胞周期调节、基因组稳定性、增殖、分化、干细胞稳态、凋亡、代谢、衰老以及响应细胞因子而修复DNA损伤。压力。在 AML 中，TP53 改变发生在 5%-12% 的新发 AML 病例中。这些突变形成了一个重要的分子亚组，即使在接受积极化疗和同种异体干细胞移植治疗的情况下，携带这些突变的患者在 AML 患者中预后最差，总生存期最短。复发性和复发性 AML 中 TP53 突变的频率增加，并且与化疗耐药相关。 AML 遗传学和生物学的进展带来了新的疗法，然而，这些药物对于 TP53 突变驱动疾病的患者的临床益处仍然很大程度上尚未被探索。本综述重点关注 TP53 突变疾病的分子特征； TP53 对白血病某些特征的影响，特别是代谢重连和免疫逃避，TP53 突变的临床重要性；以及治疗 TP53 突变疾病的临床前和临床治疗策略开发的当前进展。版权所有 © 2024 Chomczyk、Gazzola、Dash、Firmanty、George、Mohanty、Abbas 和 Baran。

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML cases. These mutations form an important molecular subgroup, and patients with these mutations have the worst prognosis and shortest overall survival among patients with AML, even when treated with aggressive chemotherapy and allogeneic stem cell transplant. The frequency of TP53-mutations increases in relapsed and recurrent AML and is associated with chemoresistance. Progress in AML genetics and biology has brought the novel therapies, however, the clinical benefit of these agents for patients whose disease is driven by TP53 mutations remains largely unexplored. This review focuses on the molecular characteristics of TP53-mutated disease; the impact of TP53 on selected hallmarks of leukemia, particularly metabolic rewiring and immune evasion, the clinical importance of TP53 mutations; and the current progress in the development of preclinical and clinical therapeutic strategies to treat TP53-mutated disease.Copyright © 2024 Chomczyk, Gazzola, Dash, Firmanty, George, Mohanty, Abbas and Baran.