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摘要: DNA甲基化和组蛋白甲基化是急性髓系白血病(acute myeloid leukemia,AML)表观遗传学调控的常见模式,针对甲基化过程的靶向治疗包括DNA甲基转移酶抑制剂、甲基化调节蛋白抑制剂及组蛋白甲基化调控蛋白抑制剂,其中DNA甲基转移酶(DNA methyltransferase,DNMT)抑制剂阿扎胞苷、地西他滨已上市进入临床,针对甲基化调节蛋白IDH1/2抑制剂也已进入Ⅱ期临床研究。此外,针对组蛋白甲基化调控蛋白EZH2、LSD1抑制剂也显示出良好体外抗白血病活性,部分已进入Ⅰ期临床研究,为AML的治疗提供新的选择。Abstract: DNA and histone lysine methylations are the main epigenetic modulatory elements in the development and progression of acute myeloid leukemia. Methylation-targeted therapy includes DNA methyltransferase, methylation modulatory protein, and histonelysine methylation inhibitors. Approved DNA methyltransferase inhibitor (demethylating agent) includes azacytidine and dicitabine, which have been used as antileukemic drug clinically. IDH1/2 inhibitor also showed effective and well tolerated in leukemic patients in phase Ⅱ clinical study. EZH2 inhibitor and LSD1 inhibitor have completed in vitro study and entered clinical trial. Targeting DNA and histone lysine methylations is an alternative approach for leukemia treatment.
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Key words:
- acute myeloid leukemia /
- DNA methylation /
- histone lysine methylation /
- therapy
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