Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival

Anne Laurence Astier, Ronghui Xu, Marek Svoboda, Esther Hinds, Olivier Munoz, Rosalie de Beaumont, Colin Daniel Crean, Theodore Gabig, Arnold Stephen Freedman

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1118-27
Number of pages10
JournalBlood
Volume101
Issue number3
DOIs
Publication statusPublished - 2003

Keywords

  • Antigens, CD29
  • Apoptosis
  • B-Lymphocytes
  • Cell Adhesion
  • Cell Communication
  • Cell Division
  • Cell Survival
  • Fibronectins
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Polylysine
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Signal Transduction
  • Time Factors
  • Tumor Cells, Cultured

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