MicroRNA Expression Profiling Identifies Activated B Cell Status in Chronic Lymphocytic Leukemia Cells

Chronic lymphocytic leukemia (CLL) is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA) expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA) identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70+ and IgVH unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.慢性淋巴细胞白血病（Chronic lymphocytic leukemia, CLL）曾被认为是一种静息淋巴细胞疾病。然而，近期研究数据提示，CLL细胞或许更接近于活化B细胞。本研究通过对38例患者的高度富集CLL细胞、9例未接受急性CpG激活处理的正常供者未转化B细胞，以及5例经急性CpG激活后的匹配B细胞进行微小RNA（microRNA, miRNA）表达谱分析，证实CLL细胞具有活化B细胞表型。基因集富集分析（Gene Set Enrichment Analysis, GSEA）显示，活化B细胞与CLL细胞的miRNA表达存在统计学显著的相似性，具体涉及miR-34a、miR-155及miR-342-3p的上调，以及miR-103、miR-181a与miR-181b的下调。此外，两种CLL特征性miRNA——miR-29c与miR-223的表达水平降低，与ZAP70阳性、IgVH未突变状态以及更短的首次治疗时间显著相关。上述研究数据表明CLL细胞具有活化B细胞表型，且提示单个miRNA的表达变化方向或可预测CLL患者的临床病程。