Genetics and Epigenetics of Hodgkin's Lymphoma

Introduction Hodgkin's lymphoma (HL) is one of the most common lymphoid malignancies in the Western world. This disease is characterized by an incidence of around ۳ new cases per ۱۰۰,۰۰۰ population per year . An important feature of HL is its age distribution, as it is not only common in the elderly, but also in young adults, making it one of the most prevalent cancers in this age group .HL is a unique type of lymphoma, as it is characterized by the presence of rare, large tumor cells called Hodgkin and Reed-Sternberg (HRS) cells. These cells, which comprise only a small fraction of the tumor mass, are considered the neoplastic cells that drive the disease . The surrounding tumor microenvironment, which consists of a large number of non-malignant inflammatory cells, also plays a crucial role in the pathogenesis of HL .The treatment of HL is considered one of the great successes in cancer therapy. The successful treatment rate is around ۸۰ to ۹۰ percent using a combination of chemotherapy and radiotherapy . Furthermore, new therapeutic approaches such as immune checkpoint inhibitors and CD۳۰-targeted antibody-drug conjugates have shown promising results in improving treatment rates and reducing long-term toxicity of conventional treatments .However, despite therapeutic success, the biology and pathogenesis of HL have remained a puzzle for a long time. The main reason for this is the rarity of the tumor cells in the involved lymph nodes, which has made their molecular analysis extremely challenging . Nevertheless, important advances in understanding the biology of HL have been made in the past few decades, which will be the focus of this review.These advances have shed light on the genetic and epigenetic alterations that drive the development and progression of HL. By unraveling the complex interplay between the malignant HRS cells and their surrounding microenvironment, researchers have gained a deeper understanding of the molecular mechanisms underlying this disease. This knowledge has not only improved our understanding of HL but has also paved the way for the development of more targeted and effective therapies. Metods Searching for articles in NCBA, Gigalib, Scopus databases and reading and reviewing articles Conclusion The genetic and epigenetic landscape of Hodgkin's lymphoma (HL) has been crucial in elucidating the underlying disease pathogenesis. Recurrent genetic alterations in key signaling pathways, such as NF-κB and JAK/STAT, have provided important insights into the molecular mechanisms drivingHL.Additionally,therecognitionofaberrantepigeneticdysregulation,includingDNAmethylationand histone modifications, has opened new avenues for targeted therapeutic interventions. Targeting these epigenetic aberrations has shown promise in preclinical and clinical studies, paving the way for more effective and personalized treatment strategies. Moving forward, the continued integration of genetic and epigenetic data will be essential for refining our understanding of HL and developing novel biomarkers and therapeutic targets to improve patient outcomes.

کلیدواژه ها:

Hodgkin's lymphoma ، Genetics ، Epigenetics ، NF-κB ، JAK/STAT