A number of preclinical and clinical trials in CLL have targeted VEGF/VEGF-R, MMP-9/CD44/VLA-4, CXCL-12/CXCR4, TNF-α/TNF-R, and IGF-1/IGF-1-R (Table 2). This evidence concerns the gene CXCL12 and B-cell chronic lymphocytic leukemia.