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.