Analysis of CLL patients that stop responding to BTKi has revealed that most develop mutations within Btk or in the substrate of BTK: Phospholipase C gamma 2 (PLCγ2) (Maddocks et al., 2015; Ahn et al., 2017; Woyach et al., 2014). This evidence concerns the gene PLCG2 and B-cell chronic lymphocytic leukemia.