In this regard, BTK inhibitors (ibrutinib and acalabrutinib) which inhibit downstream intracellular signaling involving phospholipase Cγ2 (PLCg2), and PI3K inhibitors (idelalisib) which target a critical phosphorylation step in the signaling pathway, have revolutionized the treatment of CLL. This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.