In summary, we observe a crucial role of Gαi-coupled proteins but not CXCL12-CXCR4 signals in VLA-4 mediated homing of tri12 CLL cells to BM, suggesting VLA-4 activation by a Gαi-coupled mechanism independent from CXCL12. Here, CXCL12 is linked to B-cell chronic lymphocytic leukemia.