Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
General University Hospital, Prague, Czech Republic.
Cancer Biomark. 2018;22(1):101-110. doi: 10.3233/CBM-171029.
Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction of AZA responsiveness is important for the therapy management.
Using microarrays and reverse-transcription quantitative-PCR, we analyzed microRNA (miRNA) expression in bone marrow CD34+ cells of 27 patients with higher-risk myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes before and during AZA treatment.
At baseline, we found that future overall response rate was significantly higher in patients with upregulated miR-17-3p and downregulated miR-100-5p and miR-133b. Importantly, the high level of miR-100-5p at baseline was associated with shorter overall survival (HR = 4.066, P= 0.008). After AZA treatment, we observed deregulation of 30 miRNAs in responders (including downregulation of miR-10b-5p, miR-15a-5p/b-5p, miR-24-3p, and miR-148b-3p), while their levels remained unchanged in non-responders.
Our study demonstrates that responders and non-responders have distinct miRNA patterns and that the level of specific miRNAs before therapy may predict the efficacy of AZA treatment.
阿扎胞苷（AZA）是一种用于治疗骨髓增生异常综合征的核苷类似物，预测 AZA 反应性对于治疗管理非常重要。
我们使用微阵列和逆转录定量 PCR 分析了 27 例高危骨髓增生异常综合征或伴有骨髓增生异常相关改变的急性髓系白血病患者在 AZA 治疗前后骨髓 CD34+细胞中的 microRNA（miRNA）表达。
在基线时，我们发现 miR-17-3p 上调和 miR-100-5p、miR-133b 下调的患者未来总体反应率显著更高。重要的是，基线时高水平的 miR-100-5p 与总生存期较短相关（HR=4.066，P=0.008）。在 AZA 治疗后，我们观察到应答者中存在 30 个 miRNA 的失调（包括 miR-10b-5p、miR-15a-5p/b-5p、miR-24-3p 和 miR-148b-3p 的下调），而在无应答者中其水平保持不变。
我们的研究表明，应答者和无应答者具有不同的 miRNA 模式，并且治疗前特定 miRNA 的水平可能预测 AZA 治疗的疗效。
