MicroRNA Expression Profiling Identifies Activated B Cell Status in Chronic Lymphocytic Leukemia Cells
Moffett, Howell F.
Wucherpfennig, Kai W.
Brown, Jennifer R.
Novina, Carl D.
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CitationLi, Shuqiang, Howell F. Moffett, Jun Lu, Lillian Werner, Hao Zhang, Jerome Ritz, Donna Neuberg, Kai W. Wucherpfennig, Jennifer R. Brown, and Carl D. Novina. 2011. “MicroRNA Expression Profiling Identifies Activated B Cell Status in Chronic Lymphocytic Leukemia Cells.” Edited by Venugopalan Cheriyath. PLoS ONE 6 (3). Public Library of Science (PLoS): e16956. doi:10.1371/journal.pone.0016956.
AbstractChronic 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.
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