以甲基转移酶抑制剂为基础联合治疗中高危MDS/AML研究现状

Progress in combined treatments of myelodysplastic syndrome and acute myeloid leukemia based on DNA methyltransferase inhibitors

甲基转移酶(DNMT)抑制剂通过表观遗传学调控发挥治疗作用。由于DNMT抑制剂单药治疗骨髓增生异常综合征(MDS)疗效的局限性,以DNMT抑制剂为基础的联合治疗不断被研究和试用于临床。临床试验表明,DNMTs与靶向药物如组蛋白乙酰化酶抑制剂、免疫调节剂来那度胺等的联合在治疗MDS和部分急性髓系白血病(AML)疗效优于单药治疗。而近年来与传统化疗药物的联合在中高危MDS及AML的疗效也初露端倪。但对于高危MDS及难治AML,以DNMT抑制剂为基础的联合治疗方案仍有许多问题需要进一步探索和研究。

DNA methyltransferase（DNMT） inhibitors,a prototype of epigenetic regulation, exert the therapeutic action on acute myeloid leukemia（AML） and myelodysplastic syndrome（MDS）. Due to the limited efficacy of monotherapy ofDNMT inhibitors in AML and MDS,numerous clinical trials of DNMT inhibitor-based combination modality therapies are under research. Some clinical trials indicate that DNMT inhibitors combined with either targeted drugs like histone acetylation enzyme inhibitors or immune regulator drugs like lenalidomide are superior to the monotherapy of DNMT inhibitors.In recent years,DNMT inhibitors combined with traditional chemotherapy for high-risk MDS and AML have shown some effects.However, DNMT inhibitor-based combination modality therapies for high-risk MDS and refractory AML still need researching.