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Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma
In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730322/ https://www.ncbi.nlm.nih.gov/pubmed/24216998 http://dx.doi.org/10.3390/cancers5020714 |
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author | Knecht, Hans Righolt, Christiaan Mai, Sabine |
author_facet | Knecht, Hans Righolt, Christiaan Mai, Sabine |
author_sort | Knecht, Hans |
collection | PubMed |
description | In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques at the single cell level has substantially improved our understanding of the molecular pathogenesis of HL. Gene expression profiling, comparative genomic hybridization analysis, micro-RNA expression profiling and viral oncogene sequencing have deepened our knowledge of numerous facets of H- and RS-cell gene expression deregulation. The question remains whether disturbed signaling pathways and deregulated transcription factors are at the origin of refractory/relapsing Hodgkin’s lymphoma or whether these hallmarks are at least partially related to another major factor. We recently showed that the 3D nuclear organization of telomeres and chromosomes marked the transition from H- to RS-cells in HL cell lines. This transition is associated with progression of telomere dysfunction, shelterin disruption and progression of complex chromosomal rearrangements. We reported analogous findings in refractory/relapsing HL and identified the shelterin proteins TRF1, TRF2 and POT1 as targets of the LMP1 oncogene in post-germinal center B-cells. Here we summarize our findings, including data not previously published, and propose a model in which progressive disruption of nuclear integrity, a form of genomic instability, is the key-player in refractory/relapsing HL. Therapeutic approaches should take these findings into account. |
format | Online Article Text |
id | pubmed-3730322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-37303222013-08-05 Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma Knecht, Hans Righolt, Christiaan Mai, Sabine Cancers (Basel) Article In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques at the single cell level has substantially improved our understanding of the molecular pathogenesis of HL. Gene expression profiling, comparative genomic hybridization analysis, micro-RNA expression profiling and viral oncogene sequencing have deepened our knowledge of numerous facets of H- and RS-cell gene expression deregulation. The question remains whether disturbed signaling pathways and deregulated transcription factors are at the origin of refractory/relapsing Hodgkin’s lymphoma or whether these hallmarks are at least partially related to another major factor. We recently showed that the 3D nuclear organization of telomeres and chromosomes marked the transition from H- to RS-cells in HL cell lines. This transition is associated with progression of telomere dysfunction, shelterin disruption and progression of complex chromosomal rearrangements. We reported analogous findings in refractory/relapsing HL and identified the shelterin proteins TRF1, TRF2 and POT1 as targets of the LMP1 oncogene in post-germinal center B-cells. Here we summarize our findings, including data not previously published, and propose a model in which progressive disruption of nuclear integrity, a form of genomic instability, is the key-player in refractory/relapsing HL. Therapeutic approaches should take these findings into account. MDPI 2013-06-05 /pmc/articles/PMC3730322/ /pubmed/24216998 http://dx.doi.org/10.3390/cancers5020714 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Knecht, Hans Righolt, Christiaan Mai, Sabine Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title | Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title_full | Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title_fullStr | Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title_full_unstemmed | Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title_short | Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma |
title_sort | genomic instability: the driving force behind refractory/relapsing hodgkin’s lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730322/ https://www.ncbi.nlm.nih.gov/pubmed/24216998 http://dx.doi.org/10.3390/cancers5020714 |
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