上海交通大学学报(医学版) ›› 2018, Vol. 38 ›› Issue (8): 960-.doi: 10.3969/j.issn.1674-8115.2018.08.017

• 综述 • 上一篇    下一篇

异柠檬酸脱氢酶基因突变在急性髓细胞白血病发生中的作用

李青丽,文君,闵雪洁,赵丽,赵小平   

  1. 上海交通大学医学院附属仁济医院核医学科,上海 200001
  • 出版日期:2018-08-28 发布日期:2018-09-11
  • 通讯作者: 赵小平,电子信箱:Zxp0856@sina.com。
  • 作者简介:李青丽(1992—),女,硕士生;电子信箱: 610854203@qq.com。
  • 基金资助:
    国家自然科学基金( 81372195,81572719);上海市教育委员会高峰高原学科建设计划( 20152516)

Effect of IDHgene mutation on acute myeloid leukemia

LI Qing-li, WEN Jun, MIN Xue-jie, ZHAO Li, ZHAO Xiao-ping   

  1. Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
  • Online:2018-08-28 Published:2018-09-11
  • Supported by:
    National Natural Science Foundation of China, 81372195, 81572719; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Support, 20152516

摘要: 异柠檬酸脱氢酶( isocitrate dehydrogenase,IDH)是参与三羧酸循环重要的代谢酶。近年来,在急性髓细胞白血病 (acute myeloid leukemia,AML)中 IDH成为突变最频繁的肿瘤代谢基因。与其他基因的突变不同,该基因突变后获得的新功能可催化 α-酮戊二酸( α-ketoglutarate,α-KG)产生肿瘤代谢物二羟基戊二酸( D-2-hydroxyglutarate,D-2-HG)。而细胞中升高的 D-2-HG可直接通过遗传表观调控、细胞信号转导、骨髓微环境变化等方式影响骨髓细胞的分化和增殖,诱发 AML。目前,新型的 IDH2抑制剂 AG221和 IDH1抑制剂已成为靶向治疗 AML患者中 IDH突变的临床一线药物。该文主要针对 IDH突变及其突变特点、突变产生的代谢物对 AML的形成机制、肿瘤代谢物的代谢通路以及 IDH抑制剂的研究进展进行综述。

关键词: 异柠檬酸脱氢酶, 基因突变, 急性髓细胞白血病, 肿瘤代谢物, 二羟基戊二酸, 异柠檬酸脱氢酶抑制剂

Abstract:

Isocitrate dehydrogenase (IDH) is an important metabolic enzyme involved in the tricarboxylic acid cycle. In recent years, IDH has become the most frequent tumor metabolic mutation gene in acute myeloid leukemia (AML). Unlike other mutations, it gains new functions which can catalyze α-ketoglutarate (α-KG) to produce the tumor metabolite D-2-hydroxyglutarate (D-2-HG). The increased D-2-HG in the cells can affect bone marrow cell differentiation and proliferation and induce myeloid tumorsthe genetic controls, cell signaling, bone marrow microenvironment changes and other ways. Currently, the new IDH2 inhibitors AG-221 and IDH1 inhibitors become the first-line drugs targeted therapy in patients with IDH mutations in AML. This paper focused on the mutation of IDH and its mutation characteristics, the formation mechanism of AMLthe metabolites producedmutation, the metabolic pathway of tumor metabolites and the research progress of IDH inhibitors.

Key words: isocitrate dehydrogenase (IDH), gene mutation, acute myeloid leukemia (AML), tumor metabolites, D-2-hydroxyglutarate (D-2-HG), isocitrate dehydrogenase inhibitor

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