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-kappaB (NF-kappaB) was reported to be a unique and common characteristic of H-RS cells that prevents the cells from undergoing apoptosis. NF-kappaB 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-kappaB is induced by viral latent membrane protein 1 (LMP1). Coupled with recent insights into the molecular mechanisms of activation of NF-kappaB 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-kappaB signaling pathway. This down-regulation leads to the generation of cells with H-RS phenotypes related to the clinical and histologic characteristics of HL.
Lee
Im-Soon
IS
Department of Biological Sciences, College of Sciences, Konkuk University, Seoul, Korea.
Kim
Seok Hyung
SH
Song
Hyung Geun
HG
Park
Seong Hoe
SH
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006689:Hodgkin Disease / Q000209:etiology / Q000473:pathology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000473:pathology*; D014763:Viral Matrix Proteins / Q000502:physiology
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins