Epstein-Barr virus and a cellular signaling pathway in lymphomas from

Reviewers: Kenneth Blank, MD and Leonard Farber, MD
Source: New England Journal of Medicine, Vol. 338 (20):1413

Epstein-Barr virus (EBV) is a member of the herpes virus family. It is carried by almost everyone and is usually asymptomatic. EBV has a proclivity for immune cells called B-cells, and has a clear association with benign and malignant B-cell proliferative disorders. For example, nearly all cases of African Burkitt's lymphoma is associated with EBV as are almost all cases of nasopharyngeal lymphoepithelioma. Other cancers have a weaker link to EBV; 50% of classic Hodgkin's disease is linked to EBV and a minority of breast cancers carry EBV. EBV is also associated with post-transplantation lymphoproliferative disease seen in patients who are immunosuppressed to avoid rejection of the transplanted organ. Similarly, patients with AIDS are at increased risk for EBV-associated lymphomas.

Clearly, there is an association between the EBV and B-cell lymphomas. However, proving a causative role is difficult. Most agree that EBV plays a role in the pathogenesis of these cancers, but few have been able to prove it. A paper in the May 14th issue of the New England Journal of Medicine examines the role of EBV in tumor formation.

Utilizing molecular biology techniques, David Liebowitz of the University of Chicago demonstrated that a protein- called LMP1 for latent membrane protein- produced within B-cells by EBV functions in conjunction with the cell's own signaling pathways to promote tumorigenesis. Dr. Liebowitz used tumor samples from eight patients with post-transplant lymphoproliferative disease, two patients with AIDS-associated non-Hodgkin's lymphoma and three patients with African Burkitt's lymphoma. Eight of the thirteen tumor specimens contained EBV and expressed LMP1. In these eight samples, nuclear factor-kappaB (NF-kb)- a protein found in the nucleus, which is known to promote gene transcription leading to proliferation- was activated. None of the tumor samples that were either EBV or LMP1 negative had NF-KB activated. These experiments provide further the evidence for the causal role of EBV in the development of lymphomas in immunosuppressed patients.