The ligation of CD38 induces tyrosine phosphorylation of several intracellular proteins, including spleen tyrosine kinase (SYK) in immature B-cells as well as in lamina propria T-cells.[14,15] We and others previously identified SYK as a candidate for targeted therapy in CLL due to its enhanced expression and activity and the apoptotic effects of pharmacological SYK inhibition.[16,17] Of note, ongoing clinical trials are continuing to investigate the selective SYK inhibitor entospletinib. Here, CD38 is linked to B-cell chronic lymphocytic leukemia.