MicroRNA Expression Profiling Identifies Activated B Cell Status in Chronic Lymphocytic Leukemia Cells
MicroRNA Expression Profiling Identifies Activated B Cell Status in Chronic Lymphocytic Leukemia Cells
复制标题
DOI：
10.1371/journal.pone.0016956
复制
发表时间：
2011-03-08
期刊：
影响因子：
3.7
通讯作者：
Novina, Carl D.
中科院分区：
文献类型：
--
作者：
Li, Shuqiang;Moffett, Howell F.;Novina, Carl D.
慢性淋巴细胞白血病(CLL)被认为是一种静息性淋巴细胞疾病。然而，最近的数据表明，CLL细胞可能更类似于激活的B细胞。通过对38例患者高度浓缩的CLL细胞和9例正常供者未转化的B细胞在CpG急性激活前和5例CpG急性激活后的匹配B细胞的microRNA(MiRNA)表达谱分析，我们证明CLL处于激活的B细胞状态。基因集浓缩分析(GSEA)发现活化的B细胞和CLL细胞在miRNA表达上有显著的相似性，包括miR-34a、miR-155和miR-342-3p上调，miR-103、miR-181a和miR-181b下调。此外，两个CLL标志性miRNAs miR-29c和miR-223水平的降低与ZAP70(+)和IgVH未突变状态以及首次治疗时间缩短有关。这些数据表明CLL细胞处于激活的B细胞状态，并提示单个miRNAs的变化方向可能预测CLL的临床进程。
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.