At first glance, the observation of a combinatorial enhancement of basal activity in response to more than one ibrutinib resistance mutation in a single PLCγ2 molecule, such as R665W, S707Y, and L845F suggests that the upper limit of a graded ibrutinib resistance in CLL patients may also be extended by the number of mutations co-occurring within a single PLCG2 gene of these patients. The gene discussed is PLCG2; the disease is B-cell chronic lymphocytic leukemia.