Chemokines and their ligands play a critical role in enabling chronic 
lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches 
within tissues, ultimately resulting in chemoresistance and relapse: disruption 
of these signaling pathways has become a novel therapeutic approach in CLL. The 
tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines 
from solid-organ tumours, but effects on CLL cells have not been reported. We 
studied the effect of clinically achievable concentrations of dasatinib on 
signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is 
highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK 
phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also 
significantly diminished the rapid increase in actin polymerisation observed in 
CLL cells following CXCL12 stimulation. Moreover, the drug significantly 
inhibited chemotaxis in a transwell assay, and reduced the percentage of cells 
able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib 
also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on 
cultured CLL cells. These data suggest that dasatinib, akin to other small 
molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may 
redistribute CLL cells from protective tissue niches to the peripheral blood, 
and support the investigation of dasatinib in combination strategies.