Pathogenesis and Molecular Genetics of Hodgkin Lymphoma

Abstract

Hodgkin lymphoma (HL) is separated into classical HL (cHL) and nodular lymphocyte-predominant HL (NLPHL), the latter accounting for about 5% of cases. The lymphoma cells in both forms of HL are derived from germinal center B cells. However, the Hodgkin and Reed/Sternberg (HRS) tumor cells of cHL have largely lost their B cell phenotype. Multiple mechanisms contribute to this phenomenon. Recurrent genetic lesions identified so far in HRS cells frequently affect the NF-$κ$B or JAK/STAT signaling pathways, which are constitutively active in these cells or are involved in immune evasion of HRS cells. In addition to the NF-$κ$B and JAK/STAT pathways, multiple further signaling pathways show deregulated and constitutive activity in HRS cells. Besides genetic and autocrine mechanisms, interactions with other cells in the complex microenvironment are presumably essential for the activation of these pathways.