Considering that CXCR4 hyperactivation induced several cancer-relevant pathways in B cells and confirming the association of elevated CXCR4 expression with adverse prognosis in CLL patients (Supplementary Fig. S2b), we sought to directly investigate the effect of enhanced CXCR4 signaling on B-cell lymphoproliferation and CLL development in vivo. This evidence concerns the gene CXCR4 and B-cell chronic lymphocytic leukemia.