Sun Jiewen, Yu Wenjuan, Zhang Xiang
Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, PR China.
Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, PR China.
Exp Hematol Oncol. 2025 May 22;14(1):78. doi: 10.1186/s40164-025-00668-x.
Menin inhibitors (MENINis) represent a novel and promising class of therapeutic agents for acute leukemia (AL). AL subtypes driven by overexpressed HOXA9/MEIS1, such as those characterized by KMT2A-rearranged (KMT2Ar) or NPM1-mutated (NPM1m) AL, display sensitivity to MENINi. Consequently, approximately 40-50% of acute myeloid leukemia (AML) and 5-15% of acute lymphoblastic leukemia (ALL) patients may potentially benefit from MENINi-based therapy. At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Moreover, combination therapies based on MENINis were also reported to be highly effective in refractory/relapsed, or newly diagnosed KMT2Ar- and NPM1m-AML patients. Evidently, MENINis have demonstrated a considerable efficacy in KMT2Ar- and NPM1m-AML patients with a well-tolerance. Furthermore, the therapeutic effects of venetoclax plus azacitidine or "3 + 7" regimens were further enhanced by the addition of MENINis in KMT2Ar- and NPM1m-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes.
Menin抑制剂（MENINis）是一类用于治疗急性白血病（AL）的新型且有前景的治疗药物。由过表达的HOXA9/MEIS1驱动的AL亚型，如那些以KMT2A重排（KMT2Ar）或NPM1突变（NPM1m）的AL为特征的亚型，对MENINi敏感。因此，大约40%-50%的急性髓系白血病（AML）患者和5%-15%的急性淋巴细胞白血病（ALL）患者可能潜在地受益于基于MENINi的治疗。在2024年美国血液学会（ASH）年会上，展示了关于MENINis单药治疗AL的最新临床数据，包括瑞武尼布、布勒西尼布、恩佐尼布和BN104。此外，据报道，基于MENINis的联合疗法在难治性/复发性或新诊断的KMT2Ar和NPM1m-AML患者中也非常有效。显然，MENINis在KMT2Ar和NPM1m-AML患者中已显示出相当的疗效且耐受性良好。此外，在KMT2Ar和NPM1m-AML患者中，添加MENINis可进一步增强维奈克拉加阿扎胞苷或“3+7”方案的治疗效果。因此，MENINis为AML患者提供了新的治疗前景，特别是对于那些具有高风险和预后不良的靶向亚型患者。
