Given the recent dramatic clinical impact of signal inhibitors such as ibrutinib or Idelalisib to induce high ORRs of very long duration in relapsed/refractory CLL[47] and our findings that anti-VEGF addition to CIT look promising in terms of clinical outcome for upfront CLL, it is tempting to speculate that combinations of signal inhibitors and anti-VEGF agents should be tested. This evidence concerns the gene VEGFA and B-cell chronic lymphocytic leukemia.