异柠檬酸脱氢酶突变阳性急性髓系白血病的研究进展

Research Progress of Isocitrate Dehydrogenase Mutation-Positive Acute Myeloid Leukemia--Review

异柠檬酸脱氢酶(IDH)是参与多种代谢和表观遗传过程的酶。在大约20%的急性髓系白血病(AML)患者中可检测到IDH突变,突变的IDH酶获得新的致癌酶活性,并将α-酮戊二酸(α-KG)转化为肿瘤代谢物2-羟基戊二酸(2-HG),后者在细胞中以高水平积累并阻碍α-KG依赖性酶的功能,包括表观遗传调节因子,从而导致DNA高甲基化、基因表达的异常、细胞增殖和异常分化,并促进白血病的疾病进展。IDH突变根据突变的位置和其他同时发生的基因组异常,对AML患者的预后产生不同的影响。本文将IDH阳性AML的基因改变、预后以及IDH抑制剂的最新研究进展作一概述。

Isocitrate dehydrogenase(IDH)is an enzymes involved in a variety of metabolic and epigenetic processes.IDH can be detected in approximately 20%of patients with acute myeloid leukemia(AML),the mutated IDH enzyme acquires new oncogenic enzyme activity and convertsα-ketoglutaric acid(α-KG)to the tumor metabolite 2-hydroxyglutaric acid(2-HG),which accumulates at high levels in cells and hinders the function ofαKG-dependent enzymes,including epigenetic regulators,resulting in DNA hypermethylation,abnormal gene expression,cell proliferation,and abnormal differentiation,and contributes to leukemia disease progression.IDH mutations have different effects on the prognosis of patients with AML depending on the location of the mutation and other co-occurring genomic abnormalities.This paper will review the latest research progress on the IDH positive AML gene changes,prognosis,and inhibitors.