Atallah Ehab, Garcia-Manero Guillermo
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Clin Adv Hematol Oncol. 2007 Jul;5(7):544-52.
Aberrant DNA methylation is one of the molecular hallmarks of cancer and leukemia. By repressing gene expression, it is considered a functional equivalent to the physical inactivation of tumor suppressor genes by deletions or mutations. To clinically exploit this process, compounds with DNA hypomethylating properties have been evaluated both in the laboratory and the clinic. Two such agents, 5-azacytidine and 5-aza-2'-deoxycytidine, are currently approved by the US Food and Drug Administration for the treatment of patients with myelodysplastic syndromes. Ongoing studies are evaluating alternative dosing schedules for these drugs and the activity and safety of this class of agent in combination with histone deacetylase inhibitors. Here we summarize the experience of hypomethylating agents in myelodysplastic syndromes.
异常DNA甲基化是癌症和白血病的分子特征之一。通过抑制基因表达，它被认为在功能上等同于肿瘤抑制基因因缺失或突变而发生的物理失活。为了在临床上利用这一过程，具有DNA低甲基化特性的化合物已在实验室和临床中进行了评估。两种这样的药物，5-氮杂胞苷和5-aza-2'-脱氧胞苷，目前已被美国食品药品监督管理局批准用于治疗骨髓增生异常综合征患者。正在进行的研究正在评估这些药物的替代给药方案以及这类药物与组蛋白脱乙酰酶抑制剂联合使用时的活性和安全性。在此，我们总结了低甲基化药物在骨髓增生异常综合征中的应用经验。
