- Prof. Jay A. Fishman, Principal Investigator
- Christene Huang, Research Associate
- David Scadden, Research Associate
- Stanley Martin, Research Associate
- Massachusetts General Hospital, Boston, USA
- The Role of Viral Infection in the Development of Post-Transplant Cancers
Post-transplant non-Hodgkin’s lymphoma (NHL) is a common complication following solid organ transplantation. This syndrome is termed “Post-Transplant Lymphoproliferative Disorder” or PTLD. Compared with the general population, PTLD has a poor response to conventional therapies with poor outcomes. The spectrum of disease ranges from benign B cell polyclonal, infectious mononucleosis-like disease to malignant, monoclonal lymphoma. The majority is of B lymphocyte origin although T cell, NK cell and null cell tumors are described. The predisposition to PTLD is related to inability to control infection due to viruses with direct transforming capabilities, such as Epstein-Barr virus (EBV) or Kaposi’s Sarcoma-associated herpesvirus-human herpesvirus-8 (KSHV/HHV8), immune stimulation by the allograft, and/or a variety of undefined host factors. This raises the possibility viral antigens or novel genetic species expressed during development of B cell lymphoma might become targets for diagnosis, as prognostic markers, and as targets for novel therapies for PTLD. Currently, there is no reproducible animal model to test therapeutic strategies for PTLD.
In our studies of miniature swine receiving non-myeloablative conditioning for allogeneic hematopoietic stem cell transplantation, PTLD was observed. This process appears to be driven by proliferation of a novel porcine herpesvirus porcine lymphotropic herpesvirus or PLHV-1. Many PLHV‑1 genes are homologous to those of EBV and KSHV including genes encoding putative viral oncogenes, cellular receptors and cytokines thought to be associated with malignant transformation in humans.
This project will use the miniature swine model of allogeneic stem cell transplantation to define molecular mechanisms underlying the development of virally mediated post-transplant lymphoproliferative disorders. Viral gene expression will be studied during the development of tumors using genetic microarrays. The role of other viruses in the pathogenesis of PTLD will be assessed. Novel viral and host genes detected in these studies will provide a basis for new approaches to the diagnosis and therapy of PTLD.