Gore Steven D
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA.
J Natl Compr Canc Netw. 2006 Jan;4(1):83-90. doi: 10.6004/jnccn.2006.0009.
The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and 2'-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that epigenetic modulation of gene transcription may play an important pathogenetic role in the development and expression of these diseases. Approximately 50% of patients treated with these compounds experience hematologic improvement, making these the most active single agents for unselected patients with MDS. Responses include complete and partial hematologic responses. Two randomized trials have shown that the use of these drugs significantly alters the natural history of MDS compared with supportive care. Histone deacetylase inhibitors, which may also impact the expression of genes through epigenetic mechanisms, seem to have measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors are most likely used in combination with other agents, including DNA methyltransferase inhibitors. Despite the clinical activity of these classes of drugs, there is no conclusive evidence that their clinical activity is attributable to their impact on the epigenome. Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS.
DNA甲基转移酶抑制剂5-氮杂胞苷和2'-脱氧-5-氮杂胞苷在骨髓增生异常综合征（MDS）中的临床活性表明，基因转录的表观遗传调控可能在这些疾病的发生和表现中起重要的致病作用。接受这些化合物治疗的患者中约50%出现血液学改善，使其成为未选择的MDS患者最有效的单一药物。反应包括完全和部分血液学反应。两项随机试验表明，与支持性治疗相比，使用这些药物可显著改变MDS的自然病程。组蛋白去乙酰化酶抑制剂也可能通过表观遗传机制影响基因表达，在初步研究中似乎在MDS中有可测量的活性。组蛋白去乙酰化酶抑制剂最有可能与其他药物联合使用，包括DNA甲基转移酶抑制剂。尽管这类药物具有临床活性，但尚无确凿证据表明其临床活性归因于对表观基因组的影响。这些信息对于正在进行的旨在改善MDS患者预后的更有效同类物和药物组合的开发至关重要。
