BCR activation upregulates the expression of CXCR4 in CLL cells [173], and treatment of CLL cells with ibrutinib (a BTK inhibitor) is followed by downregulation of surface CXCR4 expression and inhibition of CXCL-12/CXCR4 downstream signaling [174]. Here, CXCL12 is linked to B-cell chronic lymphocytic leukemia.