siRNA mediated SYK knockdown validated the results of the pharmacologic SYK inhibitor. Primary CLL cells (n = 4) were transfected with control siRNA or SYK-specific siRNA. After 48-hour cultures, cells were either stimulated with VCAM-1 (A) or CXCL12 (B) for 30 seconds or used for functional adhesion (C). (A) VCAM-1 stimulation up-regulated Akt phosphorylation in control transfected (P < .05), but not in SYK silenced CLL cells. n.s. indicates not significant. (B) Stimulation with CXCL12 resulted in up-regulation of pAkt by trend in nontarget siRNA but not in SYK siRNA-transfected CLL cells. (C) Flow chamber analysis revealed a clear trend to reduced adhesion capacity after SYK knockdown.