Elucidation of mechanisms of myelodysplastic syndrome progression by RNAi screening.

本研究的目的是利用rna干扰技术阐明骨髓增生异常综合征（MDS）患者耐药的机制。我们使用了来自破译公司（Cellcta, Mountain View， CA， USA）的小发夹RNA质粒文库，并将其转化为mds衍生的人类细胞系。用阿扎胞苷（MDS患者的一线药物）治疗转导细胞系30天。然后，我们分离基因组DNA，并通过下一代测序检测每个shRNA质粒的特异性条形码序列。通过比较处理和不处理阿扎胞苷的克隆组成，我们鉴定出了158个可能诱导MDS耐药的候选基因。

The aim of this study is to elucidate the mechanism of resistance to treatment in myelodysplastic syndrome (MDS) patients by using RNA-interference technologies. We employed the small-hairpin RNA plasmid library from the Decipher (Cellcta, Mountain View, CA, USA) and transduced into MDS-derived human cell lines. Transduced cell lines were treated with azacitidine, a first-line drug for MDS patients, for 30 days. Then, we isolated genomic DNA and detected specific barcode sequences for each shRNA plasmid with next-generation sequencing. By comparing the clonal composition with or without azacitidine treatment, we identified 158 candidate genes that may induce the azacitidine resistance in MDS.