Model showing the functional link between CD38 and ZAP-70 and their role in activating proliferation/survival pathways in CLL cells. (A) CD38 activation leads to the direct tyrosine phosphorylation of ZAP-70 (indicated by the black P) and this event is in turn linked to the signaling pathways controlled by CXCR4, CXCR3, and CCR7 (only CXCR4 is shown, for sake of simplification). G indicates G protein. (B) CD38 activation leads to the direct tyrosine phosphorylation of ZAP-70 (indicated by the black P), further sustaining the signal mediated by the BCR.