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伴有TP53突变的髓系肿瘤的非移植治疗方法

Nontransplant treatment approaches for myeloid neoplasm with mutated TP53.

作者信息

Mehta Ansh K, Konopleva Marina

机构信息

Department of Hematology and Oncology, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY.

Department of Hematology and Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY.

出版信息

Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):326-334. doi: 10.1182/hematology.2024000557.

Abstract

TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain a challenging spectrum of clonal myeloid disease with poor prognosis. Recent studies have shown that in AML, MDS, and MDS/AML with biallelic TP53 loss, the TP53-mutated clone becomes dominant. These are highly aggressive diseases that are resistant to most chemotherapies. The latest 2022 International Consensus Classification categorizes these diseases under "myeloid disease with mutated TP53." All treatment approaches have not improved survival rates for this disease. Many newer therapies are on the horizon, including chimeric antigen receptor T/NK-cell therapies, mutated p53 reactivators, Fc fusion protein, and monoclonal antibodies targeting various myeloid antigens. This review summarizes the current approaches for myeloid disease with TP53 mutation and provides an overview of emerging nontransplant approaches.

摘要

TP53 突变的骨髓增生异常综合征(MDS)和急性髓系白血病(AML)仍然是一类具有挑战性的克隆性髓系疾病谱,预后较差。最近的研究表明,在 AML、MDS 以及双等位基因 TP53 缺失的 MDS/AML 中,TP53 突变克隆占主导地位。这些都是高度侵袭性疾病,对大多数化疗耐药。最新的 2022 年国际共识分类将这些疾病归类为“TP53 突变的髓系疾病”。所有治疗方法都未能提高这种疾病的生存率。许多更新的疗法即将出现,包括嵌合抗原受体 T/NK 细胞疗法、突变型 p53 激活剂、Fc 融合蛋白以及靶向各种髓系抗原的单克隆抗体。本综述总结了目前针对 TP53 突变髓系疾病的治疗方法,并概述了新兴的非移植治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11665714/c74052e98b5c/hem.2024000557_s1.jpg

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