This is especially interesting when considering an SYK-based targeted therapy in CLL, since CD38 expression serves as both a negative prognostic marker and predicts poor efficacy of standard chemotherapy.[43] A SYK-targeted treatment might therefore be a valuable option when treating this subgroup of CLL patients presenting accelerated disease progression, not only by targeting the activated BCR pathway, but also by reducing CD38-mediated microenvironmental stimuli. This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.