甲基化转移酶SETD2在血液系统恶性疾病中的作用  

The role of methyltransferase SETD2 in hematological malignancies

作　　者：盛雅茹 吉忠忠 王金名 赵惠芳 何雨蔓 朱鹤[1] SHENG Yaru;JI Zhongzhong;WANG Jinming;ZHAO Huifang;HE Yuman;ZHU He(Clinical Stem Cell Research Center,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院临床干细胞研究中心,上海200127

出　　处：《肿瘤》2020年第2期137-145,共9页Tumor

基　　金：国家自然科学基金面上项目(编号:81772743).

摘　　要：含SET结构域蛋白2(SET domain-containing protein 2,SETD2)基因是表观遗传调节中的一个重要基因,其编码的SETD2蛋白是唯一一个参与组蛋白3第36位赖氨酸甲基化修饰的三甲基转移酶;对基因组的研究表明,SETD2基因在多种恶性肿瘤中发生突变。最初,SETD2在肾透明细胞癌、脑胶质瘤和乳腺癌等实体瘤中被发现。近年来,越来越多的研究表明SETD2可能在调节造血干细胞的功能以及造血系统正常发育过程中也起着重要的作用,其失活突变可促进多种血液系统恶性肿瘤(如髓系、淋巴系白血病以及淋巴瘤)的发生和发展以及耐药的产生。因此,阐明SETD2促进血液系统疾病的分子作用机制,对于血液系统疾病的诊断及治疗具有重大意义。本文就SETD2在血液系统恶性疾病的研究进展进行综述。SET domain-containing protein 2(SETD2),an epigenetic gene encoding a tri-methyltransferase of histone H3 lysine 36(H3 K36),has been found to be recurrently mutated in a variety of malignancies in the past few decades.SETD2 mutation was firstly identified in solid tumors including renal clear cell carcinoma,glioma and breast cancer,then recently found in multiple hematological malignancies.Increasing evidences have revealed that SETD2 played a pivotal role in regulating the functions of hematopoietic stem cells and the normal development of hematopoietic system.Inactivating mutations of SETD2 can promote the pathogenesis of myeloid,lymphoid leukemia and lymphoma as well as the development of therapeutic resistance.Further elucidation of the molecular mechanisms underlying SETD2-associated hematological malignancies and drug resistance is of great significance for the innovations of diagnosis and treatment methods.In this review,the progress of SETD2 in hematological malignancies are elaborated.

关 键 词：血液肿瘤 甲基转移酶类 抗药性 肿瘤 SETD2基因 

分 类 号：R733[医药卫生—肿瘤]