Detailed Information on Publication Record
2003
Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.
ASTIER, Anne, Ronghui XU, Marek SVOBODA, Esther HINDS, Olivier MUNOZ et. al.Basic information
Original name
Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.
Name in Czech
Analýza profilů genové exprese B-ALL buněk stimulovaných receptory adheze v závislosti na čase: identifikace signálních drah regulujících přežívání B-ALL buněk.
Authors
ASTIER, Anne (250 France), Ronghui XU (840 United States of America), Marek SVOBODA (203 Czech Republic, guarantor), Esther HINDS (826 United Kingdom of Great Britain and Northern Ireland), Olivier MUNOZ (250 France), Rosalie DE BEAUMONT (840 United States of America), Colin Daniel CREAN (840 United States of America), Theodore GABIG (840 United States of America) and Arnold Stephen FREEDMAN (840 United States of America)
Edition
Blood, Washington, DC, American Society of Hematology, 2003, 0006-4971
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30200 3.2 Clinical medicine
Country of publisher
Czech Republic
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 10.120
Organization unit
Faculty of Medicine
Keywords in English
Leukemia;Fibronectin;Apoptosis;Microarrays;Gene Expression Profile;Adhesion
Tags
International impact, Reviewed
Změněno: 13/10/2007 23:36, prof. MUDr. Marek Svoboda, Ph.D.
V originále
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.
In Czech
Interakce mezi B-lymfocyty a stromálními buňkami v mikroprostředí lymfatické tkáně jsou základním regulačním prvkem procesu přežívání normálních i maligních B-lymfocytů. Zvláštní úlohu zde hrají některé receptory adheze (např. alfa4beta1 integriny). Studiem signální dráhy aktivované indukcí těchto receptorů se zabývá právě tato práce. Pomocí DNA mikročipových analýz jsme vyselektovali 38 genů, které byly odlišně exprimované u B-lymfocytů s indukovanými nebo neaktivovanými integrinovými receptory. Jednalo se zejména o geny: VAV2, EPB41L1, CORO1A, FRAP1, CCT4, GJB3, FBI-I, Requiem, kaspáza-7 a další. Podařilo se nám tedy identifikovat geny zapojené do signální dráhy integrinových receptorů na modelu B-ALL buněk.