publications

Mouse models of non-Hodgkins lymphoma reveal Syk as an important therapeutic target.

Young RM, Hardy IR, Clarke RL, Lundy N, Pine P, Turner BC, Potter TA, Refaeli Y.

Blood. 2009 Mar 12;113(11):2508-16. Epub 2008 Nov 3.
Comment in: Blood. 2009 Mar 12;113(11):2371.

We have generated mouse models of Non-Hodgkin's Lymphoma (NHL) that rely on the cooperation between MYC overexpression and B-cell antigen receptor (BCR) signaling for the initiation and maintenance of B-cell lymphomas. Using these mouse models of NHL, we have focused on the identification of BCR-derived signal effectors that are important for the maintenance of NHL tumors. In the present study we concentrate on Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase required to transduce BCR-dependent signals. Using a genetic approach, we show that Syk expression is required for the survival of murine NHL-like tumors in vitro and that tumor cells deficient in Syk fail to expand in vivo. In addition, a pharmacological inhibitor of Syk was able to induce apoptosis of transformed B-cells in vitro and led to tumor regression in vivo. Finally, we show that genetic or pharmacological inhibition of Syk activity in human NHL cell lines are generally consistent with results found in the mouse models, suggesting that targeting Syk may be a viable therapeutic strategy.