Systematic name M3590
Brief description Integrin signaling signature in precursor B leukemia (PBL) cells: fibronectin (FN1) [GeneID=2335] vs control treatment with poly-L-lysine.
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12393420   Authors: Astier AL,Xu R,Svoboda M,Hinds E,Munoz O,de Beaumont R,Crean CD,Gabig T,Freedman AS
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Source species Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
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Version history 3.0: Renamed from ASTIER_FN_DIFF

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