Menin抑制剂治疗NPM1突变急性髓系白血病的研究进展

doi:10.12092/j.issn.1009-2501.2025.04.012

中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (4): 533-540.doi: 10.12092/j.issn.1009-2501.2025.04.012

Menin抑制剂治疗NPM1突变急性髓系白血病的研究进展

于晓达1，李佳璟1，王安安1，郭建刚1，刘蓓2

1兰州大学第一临床医学院，兰州 730000，甘肃；2兰州大学第一医院血液科，兰州 730000，甘肃

收稿日期:2024-05-10 修回日期:2024-07-28 出版日期:2025-04-26 发布日期:2025-04-09
通讯作者: 刘蓓，女，博士，主任医师，博士生导师，研究方向：血液系统髓系肿瘤的诊治及多药耐药的研究。 E-mail： liubeiff@163.com
作者简介:于晓达，女，硕士，研究方向：血液系统髓系肿瘤的诊治及多药耐药的研究。 E-mail： yuxd1999@163.com
基金资助:
甘肃省中医药管理局科研基金项目（GZKP-2021-28）

Recent research progress of Menin inhibitors in NPM1-mutated acute myeloid leukemia

YU Xiaoda1, LI Jiajing1, WANG Anan1, GUO Jiangang1, LIU Bei2

1The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu, China; 2Department of Hematology, the First Hosptial of Lanzhou University, Lanzhou 730000, Gansu, China

Received:2024-05-10 Revised:2024-07-28 Online:2025-04-26 Published:2025-04-09

摘要/Abstract

摘要：

核仁磷酸蛋白1（NPM1）突变是急性髓系白血病（AML）最常见的突变之一，在合并FLT3内部串联重复（FLT3-ITD）和/或DNMT3A共突变或伴不良细胞遗传学等条件下会使原本较好的预后变差。近年来，研究发现靶向Menin-KMT2A复合物的多发性内分泌腺瘤蛋白（Menin）抑制剂在NPM1突变的AML（NPM1m-AML）中可以抑制致白血病基因HOX（homeotic gene）和MEIS1（myeloid ecotropic viral integration site 1）基因的过表达，体现出显著的抗白血病活性。本文将对新型小分子靶向药物Menin抑制剂在NPM1m-AML的作用机制、临床研究以及Menin抑制剂的耐药机制进行综述，希望为 NPM1m-AML患者提供更有前景的治疗方案。

关键词: 急性髓系白血病, Menin抑制剂, NPM1突变, Menin-KMT2A复合物

Abstract:

The nucleophosmin 1 (NPM1) mutation is one of the most frequent subtypes in acute myeloid leukemia (AML). Under the conditions of FLT3-internal tandem duplications (FLT3-ITD) and/or DNMT3A co-mutations or adverse cytogenetics, the originally favorable prognosis will deteriorate. In recent years, studies have found that multiple endocrine neoplasia protein (Menin) inhibitors targeting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX (homeotic gene) and MEIS1 (myeloid ecotropic viral integration site 1) in NPM1-mutated AML, demonstrating remarkable anti-leukemia activity. This article aims to review the mechanism and clinical research of Menin inhibitors, novel small molecule targeted drugs in NPM1-mutated AML, as well as the resistance mechanism of Menin inhibitors, hoping to provide promising approaches for the subsequent treatment of NPM1-mutated AML patients.

Key words: acute myeloid leukemia, Menin inhibitors, NPM1 mutation, Menin-KMT2A complex

中图分类号:

R733.7

于晓达, 李佳璟, 王安安, 郭建刚, 刘蓓. Menin抑制剂治疗NPM1突变急性髓系白血病的研究进展[J]. 中国临床药理学与治疗学, 2025, 30(4): 533-540.

YU Xiaoda, LI Jiajing, WANG Anan, GUO Jiangang, LIU Bei. Recent research progress of Menin inhibitors in NPM1-mutated acute myeloid leukemia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(4): 533-540.

[1]	吴庭恺, 任崇崇, 张婉婉, 刘蓓. 急性髓系白血病FLT3抑制剂及耐药机制的研究进展[J]. 中国临床药理学与治疗学, 2024, 29(1): 90-98.
[2]	沈健，林颖超，朱夏吟. 小分子干扰RNA抑制HLX1表达对急性髓系白血病细胞侵袭的影响及机制探讨[J]. 中国临床药理学与治疗学, 2017, 22(6): 627-632.

Menin抑制剂治疗NPM1突变急性髓系白血病的研究进展

Recent research progress of Menin inhibitors in NPM1-mutated acute myeloid leukemia

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