INTRODUCTION: The B-cell receptor (BCR) delivers antigen-dependent and 
-independent signals that have been implicated in the pathogenesis of several 
common B-cell malignancies. Agents that can efficiently block BCR signaling have 
recently been developed and are currently being evaluated as novel targeted 
therapies. Among these, agents that inhibit the Syk kinase appear particularly 
promising in preclinical and early clinical studies.
AREAS COVERED: The manuscript provides an overview of recent findings that 
implicate Syk and the BCR signaling pathway in the pathogenesis of several 
common lymphoid malignancies. It outlines preclinical and early clinical 
experiences with the Syk inhibitor fostamatinib disodium (R788) and discusses 
various options for further clinical development of this compound.
EXPERT OPINION: Inhibitors of Syk or other components of the BCR signaling 
pathway are emerging as an exciting novel class of agents for the treatment of 
common B-cell malignancies. Future efforts should focus on defining the disease 
entities that are most likely to benefit from these agents, although 
considerable evidence is already available to pursue such studies in patients 
with chronic lymphocytic leukemia. Combinations with chemo-immunotherapy, 
treatment of early-stage disease and consolidation therapy should all be 
explored and could lead to the development of novel therapeutic approaches with 
improved efficacy, tolerability and toxicity profiles.