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

作　　者：于晓达 李佳璟 王安安 郭建刚 刘蓓[2] YU Xiaoda;LI Jiajing;WANG Anan;GUO Jiangang;LIU Bei(The First Clinical Medical School,Lanzhou University,Lanzhou 730000,Gansu,China;Department of Hematology,the First Hosptial of Lanzhou University,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]兰州大学第一医院血液科,甘肃兰州730000

出　　处：《中国临床药理学与治疗学》2025年第4期533-540,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：甘肃省中医药管理局科研基金项目(GZKP-2021-28)。

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。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.

关 键 词：急性髓系白血病 Menin抑制剂 NPM1突变 Menin-KMT2A复合物 

分 类 号：R733.7[医药卫生—肿瘤]