Bashir Qaiser, William Basem Magdy, Garcia-Manero Guillermo, de Lima Marcos
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rev Bras Hematol Hemoter. 2013;35(2):126-33. doi: 10.5581/1516-8484.20130034.
DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG) islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graft-versus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.
DNA甲基化及其他表观遗传现象似乎与多种恶性疾病的发病机制相关。DNA甲基转移酶将甲基基团添加到胞嘧啶-磷酸-鸟嘌呤（CpG）岛，导致基因启动子沉默。DNA甲基转移酶抑制剂阿扎胞苷和地西他滨对多种恶性肿瘤具有抗肿瘤活性，但大多在骨髓增生异常综合征中进行了研究。此外，这些药物具有免疫调节作用，正在异基因干细胞移植的情况下进行研究。这两种药物均已在异基因移植的围手术期使用，取得了不同程度的成功。据推测，低剂量阿扎胞苷可能会增强移植物抗白血病效应，并在髓系白血病异基因移植后维持缓解中发挥作用。同样有趣的是，这种有利作用可能在减轻移植物抗宿主病的同时出现。在此，我们对异基因移植中使用低甲基化剂进行表观遗传操纵这一迅速发展的领域进行综述。
