RNA Splicing Dysregulation in the Pathogenesis of Chronic Lymphocytic Leukemia

RNA splicing dysregulation is a hallmark of cancers, promoting the onset and progression of disease. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occurs in approximately 20% of patients. However, the underlying mechanism for splicing defects in spliceosome unmutated CLL cases remains elusive. To discover posttranscriptional regulation of RNA splicing, we performed RNA sequencing using RNA derived from B cells from 6 healthy donors and 36 CLL patients, along with MAZTER sequencing from 9 CLL patients (8 matched with RNA sequencing cohort) and B cells from 5 healthy donors. We found that CLL cells have dysregulated m6A modification sites on transcripts from splicing factors, suggesting a critical role of m6A modification in RNA splicing dysregulation.]]>

RNA剪接失调是癌症的标志性特征，可促进疾病的发生与发展。在慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）中，约20%的患者存在引发异常剪接的剪接体突变。然而，剪接体未发生突变的CLL病例中，剪接缺陷的潜在机制仍不明晰。为探究RNA剪接的转录后调控机制，本研究对6名健康供者与36名CLL患者的B细胞来源RNA开展了RNA测序，同时对9名CLL患者（其中8名与RNA测序队列匹配）以及5名健康供者的B细胞进行了MAZTER测序。研究发现，CLL细胞的剪接因子转录本上存在失调的m6A修饰位点，这表明m6A修饰在RNA剪接失调中发挥关键作用。