Molecular pathogenesis of B-cell posttransplant lymphoproliferative disorder: what do we know so far?

J Morscio,T Tousseyn,D Dierickx

doi:10.1155/2013/150835

Abstract

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.

Highlights

Posttransplant lymphoproliferative disorder (PTLD) is the most severe complication of solid organ and hematopoietic stem cell transplantation and occurs in 2%–10% of posttransplant patients
In the majority of cases, PTLD is of B-cell origin [1] rather than T-cell origin [2] and presents most commonly as extranodal non-Hodgkin lymphoma (NHL) of which diffuse large B-cell lymphoma (DLBCL) is most frequent
The etiology of PTLD is not clear 60%– 80% of the cases have been associated with Epstein-Barr Virus (EBV) infection, which has been put forward as one of the main factors contributing to PTLD development

Summary

Introduction

Posttransplant lymphoproliferative disorder (PTLD) is the most severe complication of solid organ and hematopoietic stem cell transplantation and occurs in 2%–10% of posttransplant patients. The presentation of PTLD is highly variable and ranges from benign lymphoproliferations to overt lymphoma. It has been speculated that the remaining EBV-negative PTLD cases are related to other viral infections (e.g., Human Herpes virus 8, Cytomegalovirus [3, 4]), are caused by hit-and-run infection [5] or chronic antigen stimulation by the graft or are coincidentally occurring lymphoproliferations similar to lymphomas in immunocompetent hosts [6]. In case of malignant B-cell PTLD, different types of lymphoma can arise. This variability can be partly explained by the complex development of Bcells: aberrations in each step of the developmental process can eventually contribute to lymphomagenesis. The microenvironment of the transformed lymphocyte together with the genetic background of the individual provide a particular environment that could further promote lymphomagenesis

PTLD Is a Multifactorial Disease

PTLD Presentation Ranges from Benign to Malignant Lymphoproliferations

Findings

Conclusion