Article ID Journal Published Year Pages File Type
5822521 Antiviral Research 2012 8 Pages PDF
Abstract

Epstein-Barr virus (EBV) infection and latency has been associated with malignant diseases including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and immune deficiency associated lymphoproliferative diseases. EBV-encoded latent membrane protein 2A (LMP2A) recruits Lyn and Syk kinases via its SH2-domain binding motifs, and modifies their signaling pathways. LMP2A transgenic mice develop hyperproliferative bone marrow B cells and immature peripheral B cells through modulation of Lyn kinase signaling. LMP2A/λ-MYC double transgenic mice develop splenomegaly and cervical lymphomas starting at 8 weeks of age. We reasoned that targeting Lyn in LMP2A-expressing B cells with dasatinib would provide a therapeutic option for EBV-associated malignancies. Here, we show that dasatinib inhibits B cell colony formation by LMP2A transgenic bone marrow cells, and reverses splenomegaly and tumor growth in both a pre-tumor and a syngeneic tumor transfer model of EBV-associated Burkitt lymphoma. Our data support the idea that dasatinib may prove to be an effective therapeutic molecule for the treatment of EBV-associated malignancies.

► Dasatinib inhibits B-cell colony formation by bone marrow cells from Tg-LMP2A mice. ► Dasatinib specifically decreases the spleen size of LMP2A-transgenic mice. ► Dasatinib specifically inhibits Lyn phosphorylation in LMP2A/MYC lymphomas. ► Dasatinib inhibits splenomegaly and lymphoma in LMP2A/MYC double transgenic mice.

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