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. Blood, Washington, DC: American Society of Hematology, 2003, vol. 101, No 3, p. 1118-1127. ISSN 0006-4971.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 10.120
Organization unit Faculty of Medicine
Keywords in English Leukemia;Fibronectin;Apoptosis;Microarrays;Gene Expression Profile;Adhesion
Tags adhesion, apoptosis, fibronectin, Gene Expression Profile, leukemia, microarrays
Tags International impact, Reviewed
Changed by Changed by: prof. MUDr. Marek Svoboda, Ph.D., učo 19402. Changed: 13/10/2007 23:36.
Abstract
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.
Abstract (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.
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