TP53 畸变患者是所有骨髓恶性肿瘤中风险最高的子集。 TP53突变型骨髓增生异常肿瘤（MDS）和急性髓系白血病（AML）的治疗难题源于传统化疗的难治性或复发后的复发，以及针对TP53突变细胞的研究疗法的转化成功有限。到目前为止，还没有针对这种突变子集的靶向疗法获得商业批准。因此，TP53 突变 MDS 和 AML 患者的管理计划通常由临床判断和/或医生偏好驱动，而不是由严格证据基础支持的共识指南。这种基于临床案例、证据驱动的审查突出了指导常见患者原型管理的最重要数据。本综述讨论了源自多机构经验以及以疾病为中心的联盟的一线选择的治疗菜单，并讨论了如何针对不同的患者群体优化这些一线选择。总结了关于是否应该向这些患者提供同种异体干细胞移植的争论。最后，这篇综述探讨了最近领先的研究药物（eprenetapopt、magrolimab、sabatolimab 和 idasanutlin）临床试验暂停的不幸消息，并提供了在 2025 年重振精准治疗产品线的解决方案。© 2024。作者（ s)，经 Springer Nature Limited 独家许可。

Patients with TP53 aberrations comprise the highest risk subset of all myeloid malignancies. The managerial conundrum of TP53-mutant myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) stems from refractoriness to or relapse after conventional chemotherapy, as well as the limited translational success of investigational therapies targeting TP53-mutant cells. Thus far, no targeted therapies have been commercially approved for this mutational subset. As a result, management plans for patients with TP53-mutant MDS and AML are often driven by clinical judgment and/or physician preference rather than consensus guidelines backed by a rigorous evidence basis. This clinical case-based, evidence-driven review highlights the most salient data that guides the management of commonly encountered patient prototypes. This review discusses the therapeutic menu of first-line options that derive from multi-institutional experiences as well as from disease-centric consortia and discusses how these first-line options can be optimally tailored to heterogeneous groups of patients. The debate regarding whether allogeneic stem cell transplant should be offered to these patients is summarized. Finally, this review explores the recent unfortunate news of pauses in clinical trials for the leading investigational agents - eprenetapopt, magrolimab, sabatolimab, and idasanutlin - and offers solutions toward re-invigorating the pipeline of precision therapeutics in 2025.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.