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骨髓增生异常综合征(myelodysplastic syndrome,MDS)的发病机制涉及多阶段、多因素,基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰,MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶(DNA methyltransferase,DNMT)抑制剂降低总体甲基化水平,在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类:5-氮杂胞苷(5-azacytidine,5-Aza-CdR)、地西他滨(5-Aza-2-deoxycytidine,decitabine)等核苷和核苷衍生物类抑制剂,它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善,但缓解率、疗效尚不够令人满意;肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功,为MDS去甲基化治疗药物的研究开启了一种新思路。
The pathogenesis of myelodysplastic syndrome (MDS) involves multiple stages, multiple factors, genetic alterations and epigenetic modifications may participate in this process. DNA methylation is one of the most important epigenetic modifications, MDS patients often show the overall DNA hypermethylation. Using DNA methyltransferase (DNMT) inhibitors to reduce overall methylation levels, productive clinical response and hematological improvement have been achieved in MDS patients. DNMT inhibitors can be divided into two categories: nucleosides and nucleoside derivatives such as 5-azacytidine (5-Aza-CdR) and decitabine Class inhibitors, they can improve the clinical MDR patients complete response rate, partial response rate and hematological improvement, but the remission rate, the effect is not satisfactory enough; hydralazine and other non-nucleoside inhibitors. The successful application of non-nucleoside inhibitor and magnesium valproate in the treatment of MDS opens up a new idea for the study of MDS demethylation drugs.