BTK and B-cell chronic lymphocytic leukemia: Even though most CLL patients initially respond to ibrutinib, an increasing number of patients develop resistance to the drug which is associated with mutation in the BTK gene at the ibrutinib binding site as C481S as well as mutations in the immediate downstream effector phospholipase Cγ2 (PLCγ2) (R665W and L845F) domain [7].