MicroRNA-150 Contributes to the Proficiency of B-Cell Receptor Signaling in Chronic Lymphocytic Leukemia by Regulating Expression of GAB1 and FOXP1 Genes

ABSTRACT: We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3M-bM-^@M-^Y UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome. We performed gene expression analysis on isolated leukemia cells from 100 CLL patients using the Affymetrix HG-U133 Plus 2 platform. Array data was processed by dChip software (http://www.dchip.org). No techinical replicates were performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Marek Mraz 

PROVIDER: E-GEOD-49896 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress