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

J 2014

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

MRÁZ, Marek, L.G. CHEN, L.Z. RASSENTI, E.M. GHIA, H.Y. LI et. al.

Basic information

Original name

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

Authors

MRÁZ, Marek (203 Czech Republic, guarantor, belonging to the institution), L.G. CHEN (840 United States of America), L.Z. RASSENTI (840 United States of America), E.M. GHIA (840 United States of America), H.Y. LI (840 United States of America), K. JEPSEN (840 United States of America), E.N. SMITH (840 United States of America), K. MESSER (840 United States of America), K.A. FRAZER (840 United States of America) and T.J. KIPPS (840 United States of America)

Edition

Blood, WASHINGTON, American Society of Hematology, 2014, 0006-4971

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.452

RIV identification code

RIV/00216224:14740/14:00078422

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1182/blood-2013-09-527234

UT WoS

000342618300015

Keywords in English

GENE MUTATION STATUS; DOWN-REGULATION; C-MYB; DISEASE PROGRESSION; PROTEIN EXPRESSION; CD38 EXPRESSION; CLL PATIENTS; MICRORNAS; ZAP-70; APOPTOSIS

Abstract

V originále

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.

Links

EE2.3.30.0009, research and development project

Name: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

Citovat

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. Blood. WASHINGTON: American Society of Hematology, 2014, vol. 124, No 1, p. 84-95. ISSN 0006-4971. Available from: https://dx.doi.org/10.1182/blood-2013-09-527234.

@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, 2014, vol.~124, No~1, p.~84-95. ISSN~0006-4971. Available from: https://dx.doi.org/10.1182/blood-2013-09-527234.

Detailed Information on Publication Record