BTK and B-cell chronic lymphocytic leukemia: For instance, in chronic lymphocytic leukemia, hypermorphic PLCγ2 mutations are associated with resistance to Bruton’s tyrosine kinase (BTK) inhibition by ibrutinib, which provokes constitutive downstream signaling (e.g., IP3 production and Ca2+ release) and B cell proliferation18,20,22,23.