去甲基化药物在急性髓系白血病中的临床应用进展

Clinical application of hypomethylating agents in acute myeloid leukemia

DNA甲基化作为一种重要的表观遗传修饰,严密调控着基因的表达和基因组的稳定。DNA异常甲基化可引起基因表达异常、转录失活和抑癌基因失活,从而导致肿瘤的发生,是急性髓系白血病发生的重要分子机制。去甲基化药物能够抑制DNA甲基化转移酶的活性,降低DNA甲基化水平,具有抗肿瘤作用,是急性髓系白血病目前可供选择的一线治疗方案。但因其单药治疗疗效有限,国内外学者不断通过尝试识别生物标志或将去甲基化药物与其他药物联合以期提高疗效,现已取得显著成果。

DNA methylation as an important epigenetic modification,tightly regulates gene expression and genome stability.Aberrant DNA methylation can lead to abnormal gene expression,transcription inactivation and inactivation of tumor suppressor gene,thus causing tumorigenesis that is an important molecular mechanism for the occurrence of acute myeloid leukemia(AML).Hypomethylating agents can inhibit the activity of DNA methylation transferase,reduce the level of DNA methylation and exert antitumor activities,are currently available first-line treatment options for AML.However,its monotherapy has limited efficacy.Domestic and foreign scholars have carried out a lot of studies on biomarkers or combination strategies to improve efficacy and have obtained significant results.