alpha(4)beta(1) integrin-mediated adhesion of CD34(+) cells from patients with chronic myeloid leukaemia: influence of IL-3

Interactions between integrins on haemopoietic progenitor cells and their s tromal ligands have an important role in the control of haemopoiesis. Growt h factors can modulate these interactions (so-called 'inside-out' signallin g) resulting in changes in ligand binding activity, We have studied alpha(4 )beta(1) integrin-mediated adhesion to the H120 fragment of fibronectin (wh ich contains the strongest alpha(4)beta(1) binding site) in CD34(+) cells f rom patients with chronic myeloid leukaemia (CML) and have determined the e ffect of IL-3 on the level of adhesion, Compared to normal CD34(+) cells is olated from cord blood and peripheral blood progenitor harvests (mean of 61 .4+/-14.9% of cells attached) the CML CD34(+) cells showed reduced levels o f adhesion (mean of 41.9 +/- 14.7%. P<0.05). The effect of 10 ng/ml of IL-3 resulting In reduced adhesion of normal CD34(+) cells at 30 min was absent in 6/7 patients with CML. Abnormalities of adhesion to fibronectin may thu s be related to IL-3 pathways affected by BCR-ABL. These findings will have implications for understanding the dysregulation of growth and adhesion in CML.