Department of Hematology and BMT Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
Medical School of Nankai University, 94 Weijin Road, Tianjin, 300071, China.
Ann Hematol. 2018 Nov;97(11):2025-2038. doi: 10.1007/s00277-018-3464-9. Epub 2018 Aug 6.
Azacitidine and decitabine, two hypomethylating agents, are known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who cannot endure intensive cytotoxic chemotherapy or are not eligible for transplantation. However, the treatment response rate is low. The molecular mechanisms underlying the resistance to demethylation therapy are unclear. Though a wide range of predictors of treatment response have been investigated, no consensus has been reached. It is imperative to identify certain parameters that can help distinguish between patients who will obtain a favorable outcome from demethylation therapy and those who will not. Here, we describe currently researched potential predictors based on clinical characteristics, DNA methylation, gene mutation, gene expression, microRNAs, and protein expression. Although these parameters are not currently used in clinical practice, this review provides new sights into available clinical and experimental research. Moreover, this paper provides useful information on AML/MDS management.
阿扎胞苷和地西他滨是两种低甲基化剂，已知可有效治疗无法耐受强化细胞毒性化疗或不符合移植条件的高危骨髓增生异常综合征 (MDS) 和急性髓系白血病 (AML) 患者。然而，治疗反应率较低。导致去甲基化治疗耐药的分子机制尚不清楚。尽管已经研究了广泛的治疗反应预测因子，但尚未达成共识。确定某些参数以帮助区分哪些患者将从去甲基化治疗中获得良好的结果，哪些患者不会，这一点至关重要。在这里，我们根据临床特征、DNA 甲基化、基因突变、基因表达、microRNAs 和蛋白质表达描述了目前研究的潜在预测因子。尽管这些参数目前尚未在临床实践中使用，但本综述为现有的临床和实验研究提供了新的视角。此外，本文还提供了有关 AML/MDS 管理的有用信息。
