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Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.
Astier, Anne Laurence; Xu, Ronghui; Svoboda, Marek; Hinds, Esther; Munoz, Olivier; de Beaumont, Rosalie; Crean, Colin Daniel; Gabig, Theodore; Freedman, Arnold Stephen.
Afiliação
  • Astier AL; Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Blood ; 101(3): 1118-27, 2003 Feb 01.
Article em En | MEDLINE | ID: mdl-12393420
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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Leucemia-Linfoma Linfoblástico de Células Precursoras B / Integrina beta1 / Perfilação da Expressão Gênica Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2003 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Leucemia-Linfoma Linfoblástico de Células Precursoras B / Integrina beta1 / Perfilação da Expressão Gênica Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2003 Tipo de documento: Article