Skuli Sarah, Matthews Andrew, Carroll Martin, Lai Catherine
Division of Hematology and Oncology, Department of Medicine, The University of Pennsylvania, Philadelphia, PA.
Division of Hematology and Oncology, Department of Medicine, The University of Pennsylvania, Philadelphia, PA.
Semin Hematol. 2024 Dec;61(6):449-456. doi: 10.1053/j.seminhematol.2024.10.009. Epub 2024 Nov 6.
Mutations in the tumor suppressor protein, TP53, lead to dismal outcomes in myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Recent pathological reclassifications have integrated TP53 mutated MDS and AML under a unified category of TP53 mutated myeloid neoplasms, which allows for more flexibility in treatment approaches. Therapeutic strategies have predominantly mirrored those for AML, with allogeneic stem cell transplantation emerging as critical for long-term disease control. The question remains whether there are physiological distinctions within TP53 mutated myeloid neoplasms that will significantly impact prognosis and therapeutic considerations. This review explores the unique aspects of classically defined "TP53 mutated MDS", focusing on its distinct biological characteristics and outcomes. Our current understanding is that TP53 mutated MDS and AML are globally quite similar, but as a group have unique features compared to TP53 wildtype (WT) disease. Optimizing immunotherapy and targeting vulnerabilities due to co-mutations and/or chromosome abnormalities should be the focus of future research.
肿瘤抑制蛋白TP53的突变会导致髓系恶性肿瘤（包括骨髓增生异常综合征（MDS）和急性髓系白血病（AML））的预后不佳。最近的病理学重新分类将TP53突变的MDS和AML归为TP53突变髓系肿瘤的统一类别，这使得治疗方法更具灵活性。治疗策略主要借鉴了AML的策略，异基因干细胞移植已成为长期疾病控制的关键。问题仍然是，TP53突变的髓系肿瘤内是否存在会显著影响预后和治疗考量的生理差异。本综述探讨了经典定义的“TP53突变MDS”的独特方面，重点关注其独特的生物学特征和预后。我们目前的理解是，TP53突变的MDS和AML总体上非常相似，但与TP53野生型（WT）疾病相比，作为一个群体具有独特的特征。优化免疫疗法以及针对共突变和/或染色体异常导致的脆弱性应成为未来研究的重点。
