Selective efficacy of depsipeptide in a xenograft model of Epstein-Barr virus-positive lymphoproliferative disorder. J Natl Cancer Inst 2004;96: 1447–57. www.aacrjournals.org 11145

Background: Immune-compromised individuals are at in-creased risk for developing aggressive Epstein-Barr virus (EBV)–associated lymphoproliferative disorders after pri-mary EBV infection or for reactivation of a preexisting latent EBV infection. We evaluated the effect of depsipep-tide, a histone deacetylase inhibitor, on EBV-positive lym-phoblastoid cell lines (LCLs) and Burkitt lymphoma cell lines in a mouse model and explored its mechanism of action in vitro. Methods: We studied EBV-transformed LCLs, which express a latent III (Lat-III) viral gene profile, as do some EBV-positive lymphoproliferative malignancies, and Burkitt lymphoma cell lines, which express a Lat-I viral gene profile. Cell lines were used to characterize depsipeptide-induced apoptosis, which was evaluated by flow cytometry. Flow cytometry, western blot analyses, and histone deacety