2021/02/08 by Magdalena M. Brune, Darius Juškevičius, Jasmin D. Haslbauer +2 · 1 voice · 29 citations
Medicine · #Apoptosis #Biology #Cancer research #Chronic Lymphocytic Leukemia Research #Cytokine Signaling Pathways and Interactions #Epigenetics #Gene #Gene expression #Genetics #Immune system #Immunology #Laser capture microdissection #Lymphoma #Lymphoma Diagnosis and Treatment #PI3K/AKT/mTOR pathway
paper · pdf · doi:10.3390/cancers13040682
published in Cancers 13(4), 682 (Multidisciplinary Digital Publishing Institute)
openalex publication_date 2021/02/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
BACKGROUND: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but recently developed methods (especially laser capture microdissection, flow cytometry/fluorescence-activated cell sorting) facilitated molecular investigation, elucidating the pathophysiological principles of "Hodgkin lymphomagenesis". METHODS: We reviewed the relevant literature of the last three decades focusing on the genomic landscape of classic and nodular lymphocyte predominant HL (NLPHL) and summarized molecular cornerstones. RESULTS: and MHC class I and II due to various genetic alterations. Secondly, tumor growth is promoted by permanently activated JAK/STAT signaling due to pervasive mutations of multiple genes involved in the pathway. Thirdly, apoptosis of neoplastic cells is prevented by alterations of NF-κB compounds and the PI3K/AKT/mTOR axis. Additionally, Epstein-Barr virus infection can simultaneously activate JAK/STAT and NF-κB, similarly leading to enhanced survival and evasion of apoptosis. Finally, epigenetic phenomena such as promoter hypermethylation lead to the downregulation of B-lineage-specific, tumor-suppressor and immune regulation genes. CONCLUSION: The blueprint of HL genomics has been laid, paving the way for future investigations into its complex pathophysiology.