title: MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells.
abstract: 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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Li
authors.forename: Howell F
authors.initials: HF
authors.lastname: Moffett
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.forename: Carl D
authors.initials: CD
authors.lastname: Novina
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D035683:MicroRNAs