Transcriptome characterization of chronic myeloid leukemia by RNA sequencing

To determine differentially expressed and spliced transcripts in chronic myeloid leukemia, a high throughput RNA-sequencing (RNA-seq) analysis of ten CML specimens and five normal peripheral blood samples was performed. Thousands of differentially expressed genes between CML and normal control were detected, including genes involved in ribosome and signaling pathway. Splicing alterations analysis performed by an independently developed algorithm reveals that intron retention was the most frequent alternative splicing (AS) events in all the samples. Functional groups of differentially spliced genes most highly correlated with disease phase was (blast crisis relative to chronic phase) included spliceosome and nucleotide excision repair (NER), suggesting that genes involved in these processes may have a major contribution to CML progression by affecting splicing factors and DNA damage and repair as a consequence of mis-splicing.

为探究慢性髓系白血病（chronic myeloid leukemia, CML）中差异表达与可变剪接的转录本，本研究对10例CML标本及5例正常外周血样本开展了高通量RNA测序（RNA-seq）分析。本研究共检测到数千个CML与正常对照间的差异表达基因，其中涵盖参与核糖体合成及信号通路的相关基因。通过自主开发的算法开展可变剪接分析后发现，内含子保留是所有样本中最常见的可变剪接（alternative splicing, AS）事件。与疾病分期（急变期对比慢性期）相关性最高的差异剪接基因功能富集组包括剪接体及核苷酸切除修复（nucleotide excision repair, NER）通路，这提示上述通路相关基因可能通过影响剪接因子、以及错剪接引发的DNA损伤与修复过程，在CML进展中发挥关键作用。

搜集汇总

背景与挑战

背景概述

该数据集通过RNA测序技术，分析了10个慢性髓系白血病（CML）样本和5个正常外周血样本的转录组特征，旨在识别CML中的差异表达和可变剪接转录本。研究发现数千个差异表达基因，涉及核糖体和信号通路，且内含子保留是最常见的剪接事件，剪接体相关基因与疾病进展阶段（如急变期相对于慢性期）高度相关。数据集涵盖人类血液单核细胞样本，使用Illumina NextSeq 500平台进行测序，关键词包括AS、CML、RNA-seq和hnRNPA1。