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@article{561102,
author = {Astier, Anne and Xu, Ronghui and Svoboda, Marek and Hinds, Esther and Munoz, Olivier and de Beaumont, Rosalie and Crean, Colin Daniel and Gabig, Theodore and Freedman, Arnold Stephen},
article_location = {Washington, DC},
article_number = {3},
keywords = {Leukemia;Fibronectin;Apoptosis;Microarrays;Gene Expression Profile;Adhesion},
language = {eng},
issn = {0006-4971},
journal = {Blood},
title = {Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.},
volume = {101},
year = {2003}
}
TY - JOUR
ID - 561102
AU - Astier, Anne - Xu, Ronghui - Svoboda, Marek - Hinds, Esther - Munoz, Olivier - de Beaumont, Rosalie - Crean, Colin Daniel - Gabig, Theodore - Freedman, Arnold Stephen
PY - 2003
TI - Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.
JF - Blood
VL - 101
IS - 3
SP - 1118-1127
EP - 1118-1127
PB - American Society of Hematology
SN - 00064971
KW - Leukemia;Fibronectin;Apoptosis;Microarrays;Gene Expression Profile;Adhesion
N2 - The physical interactions between B cells and stromal cells from the lymphoid tissue microenvironment are critical to the survival of normal and malignant B cells. They are principally mediated by integrins expressed on B cells and counterreceptors on stromal cells. Specifically, alpha4beta1 integrin engagement rescues B cells from physiological or drug-induced apoptosis. Therefore, in order to understand the mechanisms by which integrins prevent apoptosis in leukemia B cells, we compared the temporal gene expression profiles induced by beta1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells. Among the 38 selected differentially expressed genes, 6 genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4), and intercellular communication (GJB3) were validated by real-time quantitative polymerase chain reaction (RT-Q-PCR). Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis. We further demonstrate that Fn stimulation also inhibits caspase 3 activation but increases XIAP and survivin expression. Moreover, integrin stimulation also prevents caspase activation induced by doxorubicin. Therefore, we identified genes modulated by adhesion of human precursor B leukemia cells that regulate proliferation and apoptosis, highlighting new pathways that might provide insights into future therapy aiming at targeting apoptosis of leukemia cells.
ER -
ASTIER, Anne, Ronghui XU, Marek SVOBODA, Esther HINDS, Olivier MUNOZ, Rosalie DE BEAUMONT, Colin Daniel CREAN, Theodore GABIG and Arnold Stephen FREEDMAN. Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival. \textit{Blood}. Washington, DC: American Society of Hematology, 2003, vol.~101, No~3, p.~1118-1127. ISSN~0006-4971.
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