m^(6)A去甲基化酶在急性髓系白血病中的研究进展  

Research progress of m^(6)A demethylase in acute myeloid leukemia

作　　者：卢伟杰 曾海锋 肖业臣 LU Weiji;ZENG Haifeng;XIAO Yechen(Department of Biotechnology,Basic Medical School,Guangdong Medical University,Dongguan 523808,China;Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,Guangdong Medical University,Dongguan 523808,China)

机构地区：[1]广东医科大学基础医学院生物技术系,东莞523808 [2]广东医科大学广东省医学分子诊断重点实验室,东莞523808

出　　处：《生命的化学》2024年第1期117-124,共8页Chemistry of Life

基　　金：广东省自然科学基金面上项目(2022A1515010028);广东医科大学学科建设“冲补强”项目。

摘　　要：急性髓系白血病(acute myeloid leukemia,AML)是血液系统中常见的恶性肿瘤。肥胖相关蛋白(fat mass and obesity-associated protein,FTO)和AlkB同系物5(AlkB homolog 5,ALKBH5)在AML的发生与发展中起着重要的调控作用,两者通过介导N^(6)-甲基腺苷(N^(6)-methyladenine,m^(6)A)去甲基化的方式促进细胞增殖、抑制细胞凋亡和介导化疗药物耐受等。抑制FTO和ALKBH5的去甲基化活性能够延缓AML的发生与发展。因此,FTO和ALKBH5是治疗AML的潜在靶点。本文主要对m6A去甲基化酶在AML中发挥作用的分子机制以及通过小分子抑制剂靶向FTO和ALKBH5治疗AML的研究进展作一综述。Acute myeloid leukemia(AML)is a common malignant tumor in the blood system.Fat mass and obesity-associated protein(FTO)and AlkB homolog 5(ALKBH5)play an important regulatory role in the occurrence and development of AML.Both of them mediate N^(6)-methyladenine(m^(6)A)demethylation of glycoside,which promotes cell proliferation,inhibits apoptosis and mediates chemotherapy drug resistance.Inhibiting the demethylation activity of FTO and ALKBH5 can delay the occurrence and development of AML.Therefore,FTO and ALKBH5 are potential targets for the treatment of AML.This paper mainly reviews the molecular mechanism of the role of m^(6)A demethylase in AML and the research progress in the treatment of AML through small molecule inhibitors targeting FTO and ALKBH5.

关 键 词：肥胖相关蛋白 AlkB同系物5 急性髓系白血病 m^(6)A去甲基化 靶向治疗 

分 类 号：R733.71[医药卫生—肿瘤]