However, CLL cells treated with ibrutinib in vivo did not proliferate upon CD40/IL-21 stimulation in vitro, an effect which can be recapitulated by in vitro inhibition of either BTK, PI3K or SYK, indicating the requirement of BCR kinases in CD40-mediated proliferation (107). This evidence concerns the gene SYK and B-cell chronic lymphocytic leukemia.