LYMPHOID NEOPLASIA Lymphomas differ in their dependence on Epstein-Barr virus

Epstein-Barr virus (EBV) encodes onco-genic information and, oftentimes con-comitant with host immunosuppres-sion, gives rise to malignancies in all major categories of lymphoma defined by the World Health Organization.1 Here, we conditionally evicted the viral extrachro-mosomal genome from tumor cells in vitro to examine the role of EBV in differ-ent lymphomas, including Burkitt lym-phoma (BL) and posttransplant lympho-proliferative disorder. Cells derived from 2 canonical BLs were found to have the least dependence on the virus; some required EBV to prevent the inefficient induction of apoptosis. In contrast, cells derived from a subset of BL, Wp-restricted BL, required EBV to block a robust apoptotic program that involves the up-regulation of the proapoptotic pro-tein Bim. Wp-restricted BL cells also re-lied on the virus to promote efficient proliferation, a distinction that highlights the multiple contributions EBV makes to affect proliferation of its host cells. Like Wp-BL cells, posttransplant lymphoprolif-erative disorder cells depended on the virus to inhibit apoptosis. They further-more required the virus to drive them out of G1/G0. Together, these results reveal a graded dependence on EBV among tu-mor cells that directly correlates with the number of viral genes expressed in the tumor cell. (Blood. 2011;117(6):1977-1985