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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-05-1519. This Article Full Text (PDF) All Versions of this Article: 2002-05-1519v1 101/3/1118    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Astier, A. L Articles by Freedman, A. S Search for Related Content PubMed PubMed Citation Articles by Astier, A. L Articles by Freedman, A. S Social Bookmarking                   What's this? Submitted May 23, 2002 Accepted September 4, 2002 Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor. identification of pathways regulating B-cell survival Anne L Astier, Ronghui Xu, Marek Svoboda, Esther Hinds, Olivier Munoz, Rosalie de Beaumont, Colin D Crean, Theodore Gabig, and Arnold S Freedman* Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA Department of Biostatistical Science, Harvard School of Public Health and DFCI, Boston, MA, USA Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA Department of Medicine, Indiana University School of Medicine, Indiana, IN, USA Department of Biomedical research Institute, Long Island Jewish Health System, Manhasset, NY, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA, USA Department of Biomedical research Institute, Long Island Jewish Health System, Manhasset, NY, USA * Corresponding author; email: Arnold_Freedman{at}dfci.harvard.edu. 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 counter-receptors on stromal cells. Specifically, 4ß1 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, the temporal gene expression profiles induced by ß1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells were compared. Among the 38 selected differentially expressed genes, six genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4) and intercellular communication (GJB3) were validated by RT-Q-PCR. Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation upregulated FBI1 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020