Third and most importantly, the tremendous clinical efficacy of B-cell receptor (BCR) signaling inhibitors, such as Ibrutinib (inhibitor of Bruton’s tyrosine kinase, BTK) or Idelalisib (inhibitor of phosphoinositide 3-kinase, PI3K), in reverting CLL pathology proves the immense importance of BCR-derived survival signals for the sustainability of the CLL cells (reviewed in [1,2,3,4,11,12]). This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.