Molecular carcinogenesis in Hodgkin lymphoma: Interplay between B lymphocyte mutations and NF-κB pathway dysregulation

Abstract

Hodgkin lymphoma (HL) arises from aberrant B lymphocytes due to genetic mutations, epigenetic alterations, and persistent inflammation, leading to chronic hyperactivation of the NF-κB signaling cascade, which drives cell survival and immune evasion. The pathway regulates cell survival and immune response and is abnormally activated through an interplay between genetic mutations, epigenetic changes, and persistent inflammation. This review examines the relationship between B cell mutations and NF-κB signaling in the progression of HL. Particular focus is drawn to genetic mutations concerning Epstein-Barr virus (EBV)-related proteins, such as BCL6 and CREBBP, which are reported to cause disruptions in normal B cell formation and support aberrant cell growth. These observations suggest that genetic and epigenetic alterations protect cancer cells from apoptosis while sustaining inflammation and promoting tumor development. By integrating existing studies, this review aims to identify potential molecular targets of HL development and propose new therapeutic approaches. By better elucidating these pathways, future therapies can be designed to interfere with the mechanisms of disease advancement, holding promise for better patient care.