The AML treatment landscape has significantly changed in recent years with the approval of targeted therapies in the front-line and relapsed/refractory settings, including inhibitors of FLT3 and IDH1/2 mutations. More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Even with all this exciting progress, more targeted therapies for AML treatment are needed. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.

中文翻译：

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Menin 抑制剂治疗急性髓系白血病：未来的挑战和机遇


近年来，随着一线和复发/难治性靶向治疗的批准，包括 FLT3 和 IDH1/2 突变抑制剂，AML 治疗格局发生了重大变化。更重要的是，BCl-2 抑制剂、维奈托克和低甲基化药物或低剂量阿糖胞苷联合治疗的批准为老年、身体状况不佳的 AML 患者的一线治疗提供了前所未有的突破。即使取得了所有这些令人兴奋的进展，也需要更多针对 AML 治疗的靶向疗法。最近开发的靶向 KMT2A 重排或 NPM1 突变的 AML 的 menin 抑制剂可能代表着这些 AML 亚群中患者治疗的前景广阔的新视野。我们目前的综述将侧重于 menin 抑制剂治疗 AML 的最新进展、耐药性带来的挑战以及与 menin 抑制剂新组合的机会。