Association between Epstein‐Barr virus LMP‐1 and Hodgkin lymphoma LMP‐1 mechanisms in Hodgkin lymphoma development

Abstract

AbstractHodgkin lymphoma is histologically characterised by the presence of Hodgkin (H) and Reed‐Sternberg (RS) cells originating from germinal centre B‐cells rearranged in the IgV gene. The formation of multinucleated RS cells is a product of telomere organisation in a process initiated by telomere aggregate accumulation in mononuclear H cells and may be mediated by latent membrane protein 1 (LMP‐1) expression. LMP‐1 is the main oncoprotein of EBV and supports several tumourigenic processes. LMP‐1 may rescue proapoptotic B‐cells through downregulation of B‐cell receptor (BCR) components, mimicking and inducing multiple distinct B‐cell signalling pathways to promote proliferation and survival, such as Janus kinase‐signal transducer and activator of transcription (JAK‐STAT), nuclear factor‐kappa b (NF‐кB), and cellular MYC (c‐MYC), and inducing telomere instability mainly through Telomere repeat binding factor 2 (TRF2) downregulation to promote the formation of multinucleated RS cells. This review presents recent discoveries regarding the influence of LMP‐1 on the surviving cellular signalling, genomic instability and mecanical formation of HRS cells.