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Blood. 2014 Jul 3;124(1):84-95. doi: 10.1182/blood-2013-09-527234. Epub 2014 May 1.

miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1.

Author information

1
University of California-San Diego, Moores Cancer Center, Department of Medicine, La Jolla, CA; Central European Institute of Technology, Masaryk University, Brno, Czech Republic; and Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
2
University of California-San Diego, Moores Cancer Center, Department of Medicine, La Jolla, CA;

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 ζ-chain-associated protein of 70 kDa (ZAP-70) or that used unmutated immunoglobulin heavy chain variable (IGHV) genes, 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 genes. 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 3' untranslated regions having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that enhance B-cell receptor signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 was a significant independent predictor of longer treatment-free survival or overall survival, whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for overall survival. 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, thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.

PMID:
24787006
PMCID:
PMC4125356
DOI:
10.1182/blood-2013-09-527234
[Indexed for MEDLINE]
Free PMC Article

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