Therapeutic implications of Src independent calcium mobilization in diffuse large B-cell lymphoma

MARTINEZ MARIGNAC VERONICA; ANNETTE HOLLMANN; ALOYZ R.

Montreal

Encuentro; Second Annual LDI Scientific Retreat; 2010

Lady Davis Institute- Jewish General Hospital- McGill University

We report that 38% of primary large B-cell lymphoma (DLBCL) tested expressed active Src family kinases, which are targeted by dasatinib. The expression of active Src family of kinases (SFK) in primary DLBCL tumors correlated with unfavorable prognostic markers such as Ki67 and Mum1. Using four DLBCL cell lines we found that: dasatinib resistance was associated with distinct signaling profiles downstream of BCR activation. In particular, although Src family kinase phosphorylation was inhibited by 100?150nM dasatinib in all cell lines, this failed to inhibit BCR-mediated Blnk phosphorylation, calcium signaling and proliferation in a dasatinib resistant cell line.