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Clinical and Developmental Immunology
Volume 2013, Article ID 150835, 13 pages
Review Article

Molecular Pathogenesis of B-Cell Posttransplant Lymphoproliferative Disorder: What Do We Know So Far?

1KU Leuven, Translational Cell and Tissue Research, Leuven, Belgium
2UZ Leuven, Department of Hematology, University Hospitals KU Leuven, Leuven, Belgium
3UZ Leuven, Department of Pathology, University Hospitals KU Leuven, Leuven, Belgium

Received 7 January 2013; Revised 10 March 2013; Accepted 11 March 2013

Academic Editor: Nima Rezaei

Copyright © 2013 J. Morscio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal disease that arises in 2%–10% of solid organ and hematopoietic stem cell transplants and is most frequently of B-cell origin. This very heterogeneous disorder ranges from benign lymphoproliferations to malignant lymphomas, and despite the clear association with Epstein-Barr Virus (EBV) infection, its etiology is still obscure. Although a number of risk factors have been identified (EBV serostatus, graft type, and immunosuppressive regimen), it is currently not possible to predict which transplant patient will eventually develop PTLD. Genetic studies have linked translocations (involving C-MYC, IGH, BCL-2), various copy number variations, DNA mutations (PIM1, PAX5, C-MYC, RhoH/TTF), and polymorphisms in both the host (IFN-gamma, IL-10, TGF-beta, HLA) and the EBV genome to B-cell PTLD development. Furthermore, the tumor microenvironment seems to play an important role in the course of disease representing a local niche that can allow antitumor immune responses even in an immunocompromised host. Taken together, B-cell PTLD pathogenesis is very complex due to the interplay of many different (patient-dependent) factors and requires thorough molecular analysis for the development of novel tailored therapies. This review aims at giving a global overview of the currently known parameters that contribute to the development of B-cell PTLD.