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Genomic Landscape of Hodgkin Lymphoma

SIMPLE SUMMARY: Hodgkin lymphoma (HL) is composed of many reactive and only a few cancer cells, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. Due to the scarcity of these cells, it was difficult to perform high-throughput molecular investigations on them for a long...

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Autores principales: Brune, Magdalena M., Juskevicius, Darius, Haslbauer, Jasmin, Dirnhofer, Stefan, Tzankov, Alexandar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915917/
https://www.ncbi.nlm.nih.gov/pubmed/33567641
http://dx.doi.org/10.3390/cancers13040682
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author Brune, Magdalena M.
Juskevicius, Darius
Haslbauer, Jasmin
Dirnhofer, Stefan
Tzankov, Alexandar
author_facet Brune, Magdalena M.
Juskevicius, Darius
Haslbauer, Jasmin
Dirnhofer, Stefan
Tzankov, Alexandar
author_sort Brune, Magdalena M.
collection PubMed
description SIMPLE SUMMARY: Hodgkin lymphoma (HL) is composed of many reactive and only a few cancer cells, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. Due to the scarcity of these cells, it was difficult to perform high-throughput molecular investigations on them for a long time. With the help of recently developed methods, it is now possible to analyze their genomes. This review summarizes the genetic alterations found in HRS and LP cells that impact immune evasion, proliferation and circumvention of programmed cell death in HL. Understanding these underlying molecular mechanisms is essential, as they may be of prognostic and predictive value and help to improve the therapy especially for patients with recurrent or treatment-resistant disease. ABSTRACT: 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: Firstly, the malignant cells of HL evade the immune system by altered expression of PDL1/2, B2M 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.
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spelling pubmed-79159172021-03-01 Genomic Landscape of Hodgkin Lymphoma Brune, Magdalena M. Juskevicius, Darius Haslbauer, Jasmin Dirnhofer, Stefan Tzankov, Alexandar Cancers (Basel) Review SIMPLE SUMMARY: Hodgkin lymphoma (HL) is composed of many reactive and only a few cancer cells, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. Due to the scarcity of these cells, it was difficult to perform high-throughput molecular investigations on them for a long time. With the help of recently developed methods, it is now possible to analyze their genomes. This review summarizes the genetic alterations found in HRS and LP cells that impact immune evasion, proliferation and circumvention of programmed cell death in HL. Understanding these underlying molecular mechanisms is essential, as they may be of prognostic and predictive value and help to improve the therapy especially for patients with recurrent or treatment-resistant disease. ABSTRACT: 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: Firstly, the malignant cells of HL evade the immune system by altered expression of PDL1/2, B2M 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. MDPI 2021-02-08 /pmc/articles/PMC7915917/ /pubmed/33567641 http://dx.doi.org/10.3390/cancers13040682 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Brune, Magdalena M.
Juskevicius, Darius
Haslbauer, Jasmin
Dirnhofer, Stefan
Tzankov, Alexandar
Genomic Landscape of Hodgkin Lymphoma
title Genomic Landscape of Hodgkin Lymphoma
title_full Genomic Landscape of Hodgkin Lymphoma
title_fullStr Genomic Landscape of Hodgkin Lymphoma
title_full_unstemmed Genomic Landscape of Hodgkin Lymphoma
title_short Genomic Landscape of Hodgkin Lymphoma
title_sort genomic landscape of hodgkin lymphoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915917/
https://www.ncbi.nlm.nih.gov/pubmed/33567641
http://dx.doi.org/10.3390/cancers13040682
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