Department of Leukemia, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0428, Houston, TX 77030, USA.
Expert Rev Anticancer Ther. 2010 Jan;10(1):9-22. doi: 10.1586/era.09.164.
Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias and a propensity to transform into acute myeloid leukemia. There are few treatment options available for patients with MDS. Studies into the molecular biology of MDS have demonstrated abnormal patterns of DNA methylation that lead to silencing of tumor-suppressor genes. Hypomethylating agents are compounds that have the potential to reverse the aberrant DNA methylation and increase the expression of silenced genes, leading to cellular differentiation and/or apoptosis. Decitabine is a cytidine analogue that has activity as a hypomethylating agent and has been evaluated in the therapy of patients with high-risk MDS. Several studies have confirmed the clinical activity of low-dose decitabine in patients with high-risk MDS, leading to responses in approximately 50% of patients, with low treatment-related mortality. Responses have even been seen in patients with high-risk cytogenetic abnormalities, and some studies have demonstrated increased re-expression of genes that were previously silenced by hypermethylation, such as CDKN2B/p15INK4B. There are still some issues concerning the ideal dose and schedule of decitabine for treating patients with MDS. This article focuses on the most recent clinical studies of decitabine for therapy of MDS.
骨髓增生异常综合征（MDS）是一组异质性克隆性造血干细胞疾病，其特征为无效造血、外周血细胞减少以及向急性髓系白血病转化的倾向。MDS 患者的治疗选择有限。对 MDS 分子生物学的研究表明，异常的 DNA 甲基化模式导致肿瘤抑制基因沉默。去甲基化剂是一种具有潜在逆转异常 DNA 甲基化和增加沉默基因表达的化合物，可导致细胞分化和/或凋亡。地西他滨是一种胞嘧啶类似物，具有去甲基化剂的活性，并已在高危 MDS 患者的治疗中进行了评估。几项研究证实了低剂量地西他滨在高危 MDS 患者中的临床活性，约 50%的患者有反应，且治疗相关死亡率低。甚至在高危细胞遗传学异常的患者中也观察到了反应，一些研究表明，先前因过度甲基化而沉默的基因（如 CDKN2B/p15INK4B）重新表达增加。关于地西他滨治疗 MDS 的理想剂量和方案仍存在一些问题。本文重点介绍地西他滨治疗 MDS 的最新临床研究。
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