The upregulation of integrin signaling results in increased ligand binding and enhanced adhesion and motility that is predominantly VLA-4 directed. The integrin function of CLL cells and healthy B cells was investigated. (A) The ability of the cells to bind soluble VCAM-1 or ICAM-1 was assessed by flow cytometry after integrin activation by 3 mM MnCl₂. (A) Healthy B cells (n = 4) are able to bind significant amounts after VCAM-1 and ICAM-1 after integrin activation, whereas nontrisomy 12 CLL cells (n = 4) bind comparatively little. Trisomy 12 CLL cells (n = 4) bind an intermediate amount of these ligands consistent with their increased integrin expression. The adhesive ability and nondirectional motility of healthy and malignant B cells on VCAM-1– and ICAM-1–coated plates was examined. (B) The proportion of cells in a “spread” conformation was assessed 30 minutes after stimulation with CXCL12. Trisomy 12 CLL cells exhibit an enhanced ability to adhere to immobilized VCAM-1, but not immobilized ICAM-1. (C) This enhanced adhesion translates into improved motility on VCAM-1, but was not significantly increased on ICAM-1. Error bars in all figures represent standard error of the mean.