The molecular basis for the generation of Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma

Hodgkin's lymphoma (HL) is a lymphoid neoplasm with a low frequency of malignant tumor cells, known as Hodgkin and Reed-Sternberg (H-RS) cells, in a background of mixed cellular infiltrates. Despite extensive studies on H-RS cells, the molecular mechanisms of their growth and regulation have remained uncertain for a long period. Recently, constitutively activated nuclear factor-κB (NF-κB) was reported to be a unique and common characteristic of H-RS cells that prevents the cells from undergoing apoptosis. NF-κB triggers proliferation and provides a molecular basis for these cells' aberrant growth and cytokine gene expression. In HL pathogenesis associated with Epstein-Barr virus infection, the activation of NF-κB is induced by viral latent membrane protein 1 (LMP1). Coupled with recent insights into the molecular mechanisms of activation of NF-κB signaling in H-RS cells, this review discusses a linkage between LMP1 and HL via CD99, which has recently been reported to be down-regulated by LMP1 through the NF-κB signaling pathway. This down-regulation leads to the generation of cells with H-RS phenotypes related to the clinical and histologic characteristics of HL.