中文摘要：

目的 通过比较慢性粒细胞白血病（CML）患者骨髓的白血病干细胞（LSC）和健康人骨髓正常造血干细胞（HSC）的microRNA（miRNA）表达谱,鉴定在CML LSC表达异常的miRNAs。方法 通过磁珠法分选获得分子表型为CD34＋CD38-的CML LSC和正常HSC。使用Exiqon人miRNA芯片检测miRNA的表达情况。选取差异表达的miRNAs进行qRT-PCR验证。结果 利用Exiqon人miRNA芯片一共检测了1 900个人源miRNAs的表达情况。其中1个miRNA在CML LSC中发生显著的表达上调,46个miRNAs发生显著的表达下调。基于KEGG的pathway显著性分析显示,CML LSC表达下调的miRNAs参与的显著性信号转导通路是神经营养因子信号通路。qRT-PCR检测miR-584-5p、miR-675-3p和miR-431-5p的表达情况与miRNA芯片检测结果一致。结论 鉴定了在人CML LSC中表达异常的miRNAs,为miRNA在CML LSC中的潜在应用奠定基础。

英文摘要：

Objective To identify the novel miRNAs in leukemia stem cells （LSC） by comparing the miRNA expression profile between LSC from CML patients and hematopoietie stem cell （HSC） from healthy donors. Methods HSC - enriched fractions （CD34 ＋ CD38- ） were isolated from mononuclear cells from BM from 4 patients with CML in chronic phase as well as from 3 healthy donors using immunomaguetic microbeads method. The miRNA expression was analyzed with Exiqon miRNA profiling assay. The qRT- PCR was performed to validate the novel miRNAs in LSC. Results The miRNA array showed that one miRNA was remarkably up - regulated in LSC and 46 miRNAs were obviously down - regu- lated. Based on significant KEGG pathway analysis, the down - regulated miRNAs were mainly participated in neurotropic factor transduced signaling pathway. The qRT - PCR of miR - 584 - 5p, miR - 675 - 3p and miR - 431 - 5p validated the microarray analysis. Conclusion A number of novel, aberrantly expressed miRNAs in CML LSC are identified, and thus providing the basis for a promising therapeutic approach to CML LSC.