Epstein–Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma
Aisling M. Ross,
Ciara I. Leahy,
Fiona Neylon,
Jana Steigerova,
Patrik Flodr,
Martina Navratilova,
Helena Urbankova,
Katerina Vrzalikova,
Lucia Mundo,
Stefano Lazzi,
Lorenzo Leoncini,
Matthew Pugh,
Paul G. Murray
Affiliations
Aisling M. Ross
Health Research Institute and School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
Ciara I. Leahy
Health Research Institute and School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
Fiona Neylon
Health Research Institute and School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
Jana Steigerova
Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olmouc, 775 15 Olomouc, Czech Republic
Patrik Flodr
Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olmouc, 775 15 Olomouc, Czech Republic
Martina Navratilova
Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olmouc, 775 15 Olomouc, Czech Republic
Helena Urbankova
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky Univesity and University Hospital Olomouc, 779 00 Olomouc, Czech Republic
Katerina Vrzalikova
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
Lucia Mundo
Health Research Institute and School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
Stefano Lazzi
Department of Medical Biotechnologies, Section of Pathology, University of Siena, 53100 Siena, Italy
Lorenzo Leoncini
Department of Medical Biotechnologies, Section of Pathology, University of Siena, 53100 Siena, Italy
Matthew Pugh
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
Paul G. Murray
Health Research Institute and School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
Epstein–Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.
