The effect of R406 was greatest in cells with high levels of Syk that were Un-IgVH and expressed ZAP-70.16 However, R406 had no effect on the phosphorylation of other tyrosine kinases, such as ZAP-70.16 Recent evidence has indicated that these findings are clinically relevant as the pro-drug for R406, fostamatinib disodium (FosD), is clinically active in CLL patients.17 Two novel Syk inhibitors, PRT318 and P505-15, have recently been shown to suppress CLL activation and migration in vitro. Here, ZAP70 is linked to B-cell chronic lymphocytic leukemia.