BCR ABL EXPRESSION STIMULATES INTEGRIN FUNCTION IN HEMATOPOIETIC-CELLLINES/

Cell adhesion to the extracellular matrix is largely mediated by adhes ion molecules of the integrin family and is often diminished upon onco genic transformation. However, we show here that the chronic myelogeno us leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 i ntegrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-depen dent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell bindi ng to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not t o increased surface expression. In parallel, Bcr/Abl stimulated cell a dhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 func tion directly correlated with induction of Bcr/Abl tyrosine kinase act ivity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulat es integrin-dependent cell adhesion, by a mechanism involving increase d ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precu rsor cells from chronic myelogenous leukemia patients also showed incr eased adhesion to fibronectin.