Bohl Stephan R, Bullinger Lars, Rücker Frank G
a Department of Internal Medicine III , University Hospital Ulm , Ulm , Germany.
b Department of Hematology, Oncology and Tumorimmunology , Charité University Medicine Berlin , Berlin , Germany.
Expert Rev Hematol. 2018 May;11(5):361-371. doi: 10.1080/17474086.2018.1453802. Epub 2018 Mar 27.
The majority of patients with acute myeloid leukemia (AML) are older and exhibit a poor prognosis even after intensive therapy. Inducing differentiation and apoptosis of leukemic blasts by DNA-hypomethylating agents, like e.g. azacytidine (AZA) and decitabine (DAC), represent well-tolerated alternative treatment approaches. Both agents show convincing response as single agents in AML. However, there is a lack of knowledge regarding molecular mechanisms and predictive biomarkers for these agents. Areas covered: This review will (i) provide an overview of the current knowledge of molecular mechanisms underlying the action of these drugs, (ii) report promising predictive biomarkers, (iii) elude on new combined treatment options, and (iv) discuss novel approaches to improve outcomes. A literature search was performed using PubMed to find recent major publications, which provide biological and clinical research about epigenetic therapy in AML patients. Expert commentary: Numerous studies have demonstrated that HMA therapy with AZA or DAC may lead to significant response rates, even in pre-treated patients. Nevertheless, there is still an unmet need to further improve outcome in elderly AML patients. Therefore, novel treatment combinations are needed and some of them, such as AZA plus venetoclax, already show promising results.
大多数急性髓系白血病（AML）患者年龄较大，即使经过强化治疗，预后也较差。通过DNA低甲基化剂，如阿扎胞苷（AZA）和地西他滨（DAC）诱导白血病原始细胞分化和凋亡，是耐受性良好的替代治疗方法。这两种药物在AML中作为单一药物均显示出令人信服的疗效。然而，对于这些药物的分子机制和预测性生物标志物尚缺乏了解。涵盖领域：本综述将（i）概述这些药物作用的分子机制的现有知识，（ii）报告有前景的预测性生物标志物，（iii）回避新的联合治疗选择，以及（iv）讨论改善治疗结果的新方法。使用PubMed进行文献检索，以查找近期的主要出版物，这些出版物提供了关于AML患者表观遗传治疗的生物学和临床研究。专家评论：大量研究表明，使用AZA或DAC进行HMA治疗可能会导致显著的缓解率，即使在预处理患者中也是如此。然而，老年AML患者的治疗结果仍有进一步改善的未满足需求。因此，需要新的治疗组合，其中一些，如AZA加维奈托克，已经显示出有前景的结果。
