Abstract
Epstein–Barr virus (EBV) infection is correlated with several lymphoproliferative disorders, including Hodgkin disease, Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disorder (PTLD). The oncogenic EBV is present in 80% of PTLD. EBV infection influences immune response and has a causative role in the oncogenic transformation of lymphocytes. The development of PTLD is the consequence of an imbalance between immunosurveillance and immunosuppression. Different approaches have been proposed to treat this disorder, including suppression of the EBV viral load, reduction of immune suppression, and malignant clone destruction. In some cases, upfront chemotherapy offers better and durable clinical responses. In this work, we elucidate the clinicopathological and molecular-genetic characteristics of PTLD to clarify the biological differences of EBV(+) and EBV(–) PTLD. Gene expression profiling, next-generation sequencing, and microRNA profiles have recently provided many data that explore PTLD pathogenic mechanisms and identify potential therapeutic targets. This article aims to explore new insights into clinical behavior and pathogenesis of EBV(–)/(+) PTLD with the hope to support future therapeutic studies.
Highlights
The World Health Organization (WHO) classification of lymphoid malignancies considers four major diagnostic post-transplant lymphoproliferative disorder (PTLD) categories: early lesions, polymorphic PTLD that could be either polyclonal or monoclonal, Hodgkin lymphoma (HL), and monomorphic PTLD of which diffuse large B-cell lymphoma is most common [1].PTLD can occur in 20% of hematopoietic stem cell (HSC) and solid organ transplant (SOT) recipients.PTLD is associated with Epstein–Barr virus (EBV) infection in 60–80% of cases
In PTLD, EBV(+), B-cell lymphoma revealed different microRNA profiles, compared with normal B cells or EBV lymphoblastoid cell lines generated in vitro [33, 34]. These considerations seem to suggest that the pathogenesis of EBV(–) PTLD is to be considered much more similar to that of IC-diffuse large B-cell lymphoma (DLBCL) and that it is less influenced by posttransplantation factors
In recent years, increasing understanding of the biologic and molecular PTLD pathogenesis has resulted in new therapeutic approaches and improved outcomes for these patients
Summary
The World Health Organization (WHO) classification of lymphoid malignancies considers four major diagnostic post-transplant lymphoproliferative disorder (PTLD) categories: early lesions, polymorphic PTLD that could be either polyclonal or monoclonal, Hodgkin lymphoma (HL), and monomorphic PTLD of which diffuse large B-cell lymphoma is most common [1]. In PTLD, EBV(+), B-cell lymphoma revealed different microRNA profiles, compared with normal B cells or EBV lymphoblastoid cell lines generated in vitro [33, 34] These considerations seem to suggest that the pathogenesis of EBV(–) PTLD is to be considered much more similar to that of IC-DLBCL and that it is less influenced by posttransplantation factors. Despite these differences, the fact that some EBV(–) PTLD respond well to reduction of immunosuppression to EBV(+) PTLD remains to be clarified [35]. We want to illustrate the genomic complexity of EBV(+) and EBV(–) PTLD through the integration of different genomic approaches that have significantly improved our understanding of the genetic landscape of these disorders (Table 3)
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