In addition, BCR signaling in primary CLL cells through ZAP70 up-regulated CCR7 via an extracellular signal-regulated kinase (ERK)-1/2-dependent mechanism (59) although similar results were not seen in ZAP-70-overexpressing OSU-CLL cell line (87) and a recent study showed no regulation of CCR7 protein levels in CLL cells after IgM and IgD stimulation while CXCR4 and CXCR5 were down-regulated (64). This evidence concerns the gene CD40LG and B-cell chronic lymphocytic leukemia.