《生命科学》 2022, 34(5): 489-495

组蛋白修饰异常在伴MLL重排白血病发生中的作用及靶向治疗进展

俞繁华¹ , 洪耀南¹ , 叶宝东^1,2 , 周郁鸿^1,2 , 吴迪炯^1,2,*

¹浙江中医药大学第一临床医学院，杭州 310053 ²浙江中医药大学附属第一医院血液科，杭州 310006

摘　要：

MLL 基因重排(MLL rearrangement, MLL-r) 是导致混合谱系白血病(mixed linage leukemia, MLL) 发生的关键因素，通常被认为是急性白血病的不良预后标志。由于MLL-r 白血病具有较低的存活率和缺乏有效的靶向治疗，从而引起了人们对该恶性肿瘤的广泛研究。大量的证据表明，表观遗传修饰能够调控由MLL 融合蛋白介导的异常基因表达程序，直接或间接地参与MLL-r 白血病的发生。近年来的研究提示，组蛋白修饰异常在疾病发病中发挥重要作用。与遗传变化相反，组蛋白修饰通常是可逆的，这种特有的可逆性为利用组蛋白修饰酶特定抑制剂进行靶向治疗提供了潜在途径。该文将对组蛋白修饰在MLL-r 白血病发病机制及组蛋白靶向治疗方面的研究进展予以综述。

通讯作者：吴迪炯 , Email:wudijiong@zcmu.edu.cn

Role of abnormal histone modifications in the development and targeted therapy of leukemia with MLL-rearrangement

YU Fan-Hua¹ , HONG Yao-Nan¹ , YE Bao-Dong^1,2 , ZHOU Yu-Hong^1,2 , WU Di-Jiong^1,2,*

¹The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China ²Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China

Abstract:

MLL rearrangement (MLL-r) is a critical factor in mixed linage leukemia (MLL) and is generally considered as a poor prognosis marker in acute leukemia. Due to the low survival rate of MLL-r leukemia and the lack of effective targeted therapies, extensive research has been conducted on this malignancy. There are abundant evidences showed that epigenetic modifications regulate the abnormal gene expression mediated by MLL fusion protein and are directly or indirectly involved in the occurrence of MLL-r leukemia. Recent studies have demonstrated the important role of histone-modification abnormalities in the pathogenesis of diseases. In contrast to genetic changes, histone modifications are usually reversible, and due to their unique reversibility, potential targeted therapies against specific inhibitors of histone-modifying enzymes are condiderable. In this paper, we reviewed the research progress of histone modifications in the pathogenesis and targeted therapy of MLL-r leukemia.

Communication Author：WU Di-Jiong , Email:wudijiong@zcmu.edu.cn