BACKGROUND: Mantle cell lymphoma (MCL) is currently an incurable entity, and new 
therapeutic approaches are needed. We have applied a high-throughput 
phospho-proteomic technique to MCL cell lines to identify activated pathways and 
we have then validated our data in both cell lines and tumor tissues.
METHODS: PhosphoScan analysis was performed on MCL cell lines. Results were 
validated by flow cytometry and western blotting. Functional validation was 
performed by blocking the most active pathway in MCL cell lines.
RESULTS: PhosphoScan identified more than 300 tyrosine-phosporylated proteins, 
among which many protein kinases. The most abundant peptides belonged to 
proteins connected with B-cell receptor (BCR) signaling. Active BCR signaling 
was demonstrated by flow cytometry in MCL cells and by western blotting in MCL 
tumor tissues. Blocking BCR signaling by Syk inhibitor piceatannol induced 
dose/time-dependent apoptosis in MCL cell lines, as well as several 
modifications in the phosphorylation status of BCR pathway members and a 
collapse of cyclin D1 protein levels.
CONCLUSION: Our data support a pro-survival role of BCR signaling in MCL and 
suggest that this pathway might be a candidate for therapy. Our findings also 
suggest that Syk activation patterns might be different in MCL compared to other 
lymphoma subtypes.