Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2. These recurrent mutations in key metabolic enzymes lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes leukemogenesis through a block in normal myeloid differentiation. Since this discovery, selective oral inhibitors of mutant IDH1 and IDH2 have subsequently been developed and are now approved as single agent therapy, based on clinical efficacy observed within the original first-in-human trials. The investigation of IDH inhibitors in combination with standard therapies such as azacytidine, with intensive chemotherapy, and with other small molecule targeted therapies in rational combinations are currently under evaluation to further improve upon clinical efficacy.

急性髓细胞白血病是一种遗传异质性血液系统恶性肿瘤；大约 20% 的 AML 在异柠檬酸脱氢酶 ( IDH ) 基因IDH1或IDH2中存在突变. 这些关键代谢酶的反复突变导致产生致癌代谢物 2-羟基戊二酸，通过阻断正常骨髓分化促进白血病发生。自从这一发现以来，基于在最初的首次人体试验中观察到的临床疗效，随后开发了突变 IDH1 和 IDH2 的选择性口服抑制剂，现在被批准为单药治疗。目前正在评估 IDH 抑制剂与标准疗法（如氮杂胞苷）、强化化疗以及其他小分子靶向疗法的合理组合的研究，以进一步提高临床疗效。