Interestingly, ibrutinib impaired CLL cell proliferation in the HS5CD40L,IL-4,IL-21 cocultures, but acalabrutinib did not, and this is likely due to the off-target activity of ibrutinib against JAK3 (IC50: 240 nM), which is required for interleukin signaling (40). This evidence concerns the gene IL21 and B-cell chronic lymphocytic leukemia.