Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
PLoS One. 2011 Mar 8;6(3):e16956. doi: 10.1371/journal.pone.0016956.
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 IgV(H) 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（CLL）被认为是静止淋巴细胞的疾病。然而，最近的数据表明，CLL 细胞可能更类似于活化的 B 细胞。我们使用来自 38 名患者和 9 名正常供体未经急性 CpG 激活的未转化 B 细胞以及 5 个匹配的急性 CpG 激活后的 B 细胞的高度富集的 CLL 细胞的 microRNA（miRNA）表达谱，证明了 CLL 的活化 B 细胞状态。基因集富集分析（GSEA）在激活的 B 细胞和 CLL 细胞之间的 miRNA 表达中发现了统计学上显著的相似性，包括 miR-34a、miR-155 和 miR-342-3p 的上调以及 miR-103、miR-181a 和 miR-181b 的下调。此外，两种 CLL 特征 miRNA miR-29c 和 miR-223 的水平降低与 ZAP70（+）和 IgV（H）未突变状态以及首次治疗时间较短有关。这些数据表明 CLL 细胞具有活化的 B 细胞状态，并表明单个 miRNA 的变化方向可能预测 CLL 的临床病程。
