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

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Authors	MRÁZ Marek CHEN L.G. RASSENTI L.Z. GHIA E.M. LI H.Y. JEPSEN K. SMITH E.N. MESSER K. FRAZER K.A. KIPPS T.J.
Year of publication	2014
Type	Article in Periodical
Magazine / Source	Blood
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://www.bloodjournal.org/content/124/1/84
Doi	http://dx.doi.org/10.1182/blood-2013-09-527234
Field	Oncology and hematology
Keywords	GENE MUTATION STATUS; DOWN-REGULATION; C-MYB; DISEASE PROGRESSION; PROTEIN EXPRESSION; CD38 EXPRESSION; CLL PATIENTS; MICRORNAS; ZAP-70; APOPTOSIS
Description	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 zeta-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.
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