Delving deeper into the pathogenesis and genomics of posttransplant diffuse large B-cell lymphoma

Abstract

Posttransplant lymphoproliferative disorders (PTLDs) are a well-known complication of solid organ transplantation and allogeneic hematopoietic stem cell transplantation. The diffuse large B-cell lymphoma subtype (PT-DLBCL) is the most frequent monomorphic PTLD and is associated with poor prognosis. Transplant recipients have an increased risk of abnormal proliferation of lymphoid cells because of diminished immune surveillance. In about 60% of the cases, Epstein-Barr virus infection seems to contribute to the cancer phenotype. Although clinical and research interest in the disorder has increased during the last two decades, the pathology of the disease remains largely elusive. In this review, we summarize current knowledge of PT-DLBCL pathogenesis, and we discuss how a better understanding of PT-DLBCL can lead to improved diagnostics and therapeutic strategies.

Figure 1

Latent EBV antigens and the cancer phenotypes to which they contribute. EBV infects the host's B‐cells and circularizes its DNA to establish chronic latency. The infected B‐cell expresses different latent antigens depending on its latency stage. Latency III is characterized by the expression of EBNA1, EBNA2, EBNA3A, EBNA3C, EBNA‐LP, LMP1, and LMP2. This stage is found in naive B‐cells of healthy virus carriers, from which diffuse large B‐cell lymphoma (DLBCL) can emerge in the posttransplant setting. Viral gene expression in latency II includes EBNA1, LMP1, and LMP2. It is found in germinal center B‐cells and can lead to the development of Hodgkin lymphoma. EBV persists in memory B‐cells without viral antigen expression (latency 0) or transient EBNA1 expression (latency I), which can develop into Burkitt lymphoma (BL).