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@article{1216834,
author = {Mráz, Marek and Chen, L.G. and Rassenti, L.Z. and Ghia, E.M. and Li, H.Y. and Jepsen, K. and Smith, E.N. and Messer, K. and Frazer, K.A. and Kipps, T.J.},
article_location = {WASHINGTON},
article_number = {1},
doi = {http://dx.doi.org/10.1182/blood-2013-09-527234},
keywords = {GENE MUTATION STATUS; DOWN-REGULATION; C-MYB; DISEASE PROGRESSION; PROTEIN EXPRESSION; CD38 EXPRESSION; CLL PATIENTS; MICRORNAS; ZAP-70; APOPTOSIS},
language = {eng},
issn = {0006-4971},
journal = {Blood},
title = {miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1},
url = {http://www.bloodjournal.org/content/124/1/84},
volume = {124},
year = {2014}
}
TY - JOUR
ID - 1216834
AU - 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.
PY - 2014
TI - miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1
JF - Blood
VL - 124
IS - 1
SP - 84-95
EP - 84-95
PB - American Society of Hematology
SN - 00064971
KW - GENE MUTATION STATUS
KW - DOWN-REGULATION
KW - C-MYB
KW - DISEASE PROGRESSION
KW - PROTEIN EXPRESSION
KW - CD38 EXPRESSION
KW - CLL PATIENTS
KW - MICRORNAS
KW - ZAP-70
KW - APOPTOSIS
UR - http://www.bloodjournal.org/content/124/1/84
L2 - http://www.bloodjournal.org/content/124/1/84
N2 - 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.
ER -
MRÁZ, Marek, L.G. CHEN, L.Z. RASSENTI, E.M. GHIA, H.Y. LI, K. JEPSEN, E.N. SMITH, K. MESSER, K.A. FRAZER and T.J. KIPPS. miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1. \textit{Blood}. WASHINGTON: American Society of Hematology, vol.~124, No~1, p.~84-95. ISSN~0006-4971. doi:10.1182/blood-2013-09-527234. 2014.
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