Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, Poland.
Curr Cancer Drug Targets. 2011 Sep;11(7):837-48. doi: 10.2174/156800911796798940.
Epigenetic changes play an important role in cancer pathogenesis. Hypermethylation of DNA generally results in decreased expression of tumor suppressor genes and defective cell cycle control. This is a hallmark of myelodysplastic syndromes (MDS) and acute myeloid leukemia. Fortunately, epigenetic changes are potentially reversible and thus remain an attractive target for anticancer therapy. Inhibitors of DNA methyltransferase cause demethylation of DNA and exert their activity in myelodysplastic syndromes and acute myeloid leukemia with good safety profile. Decitabine and azacytidine are approved for treatment of patients with high-risk MDS. Demethylating agents seem to be the best choice for elderly patients with myelodysplastic syndromes and acute myeloid leukemia, even in case of high risk cytogenetic changes in the karyotype. The mechanisms of action, pharmacokinetics and antileukemic activity of azacytidine and decitabine are the subjects of this review.
表观遗传改变在癌症发病机制中起重要作用。DNA 的高甲基化通常导致肿瘤抑制基因表达减少和细胞周期控制缺陷。这是骨髓增生异常综合征 (MDS) 和急性髓系白血病的一个标志。幸运的是，表观遗传改变具有潜在的可逆性，因此仍然是癌症治疗的一个有吸引力的靶点。DNA 甲基转移酶抑制剂可引起 DNA 去甲基化，并在骨髓增生异常综合征和急性髓系白血病中具有良好的安全性发挥作用。地西他滨和阿扎胞苷已被批准用于治疗高危 MDS 患者。去甲基化药物似乎是骨髓增生异常综合征和急性髓系白血病老年患者的最佳选择，即使在核型中存在高危细胞遗传学改变的情况下也是如此。阿扎胞苷和地西他滨的作用机制、药代动力学和抗白血病活性是本综述的主题。
