Wong Terrence N, Link Daniel C
Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI.
Division of Oncology, Washington University School of Medicine, St Louis, MO.
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):321-325. doi: 10.1182/hematology.2024000556.
TP53 is mutated in 10 to 15% of cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and is associated with a previous exposure to cytotoxic therapy, complex cytogenetic abnormalities, and a poor prognosis. Recent data have established the importance of TP53-mutant allele status, the determination of which requires specific genetic testing. Compared with monoallelic disease, multihit TP53-mutant AML/MDS is associated with chromosomal abnormalities and decreased overall survival. Most TP53 mutations are missense mutations that localize to the DNA binding domain. Hot-spot mutations involving residues R175, Y220, G245, R248, R273, or R282 represent approximately 35% of all TP53 missense mutations in AML/MDS. There is evidence that these hot-spot mutations may have dominant negative or gain-of-function properties. Here we review this evidence and discuss its potential impact on patient outcomes and clinical management.
在10%至15%的急性髓系白血病（AML）或骨髓增生异常综合征（MDS）病例中，TP53发生突变，且与先前接受细胞毒性治疗、复杂的细胞遗传学异常以及不良预后相关。近期数据已证实TP53突变等位基因状态的重要性，而确定该状态需要进行特定的基因检测。与单等位基因突变疾病相比，多重打击的TP53突变AML/MDS与染色体异常及总生存率降低相关。大多数TP53突变是错义突变，定位于DNA结合域。涉及残基R175、Y220、G245、R248、R273或R282的热点突变约占AML/MDS中所有TP53错义突变的35%。有证据表明，这些热点突变可能具有显性负性或功能获得性特性。在此，我们回顾这一证据，并讨论其对患者预后和临床管理的潜在影响。
