骨髓增生异常综合征表观遗传学治疗进展

Development of epigenetic treatment in myelodysplastic syndromes

表观遗传改变与基因改变有一个重要的区别就是表观遗传改变是可逆的，通过使用相应的表观遗传药物可使沉默的抑癌基因重新表达。骨髓增生异常综合征（MDS）的表观遗传治疗已经取得了很大的发展，当前应用于临床的表观遗传药物主要包括DNA去甲基化药物和去乙酰化酶抑制剂。得到FDA批准上市的DNA去甲基化药物5-氮杂胞苷和地西他滨均为MDS治疗药物，可作为中高危患者尤其是不能耐受化疗的老年患者重要的治疗选择；去乙酰化酶抑制剂如丙戊酸等目前在治疗MDS中大多处于I期临床试验阶段，可能在治疗低危MDS中有一定价值，但其剂量和治疗效果尚需进一步评估；去甲基化药物和去乙酰化抑制剂二者联用治疗MDS可能具有协同作用，但目前的临床试验尚不能证实其优于去甲基化药物的单用，仍需大样本的临床病例和合理的治疗方案来验证其安全有效性。

It have been known that many epigenetic alterations palyed an important role in development of myelodysplastic syndromes（MDS）. In contrast to genetic alterations, epigenetic alterations could be in principle pharmacologically reversed. Application of epigenetic drugs can reactivate inactivated suppressor genes. Epigenetic drugs mainly include demethylating agents and histone deacylase （HDAC） inhibitors, which are available in treatment. 5-AZA and decitabine as DNA demethylation agents have been approved by FDA of treatment in intermediate or high risk MDS, especially those old patients who are resistant to chemotherapy. HDAC inhibitors such as valproic acid are mostly employed in phase I trial, probably effective in treating low risk MDS, but treatment schedules and curative effects still have to be evaluated. The combination of demethylation agents and HDAC inhibitors may result in synergistic activity, but its therapeutic effect seems not to be superior to monotherapy of demethylation agents in current clinical trials, and it still need new clinical trials containing more cases and rational treatment schedules to identify safety and effect of combination.