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Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis

The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant...

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Autores principales: Brune, Verena, Tiacci, Enrico, Pfeil, Ines, Döring, Claudia, Eckerle, Susan, van Noesel, Carel J.M., Klapper, Wolfram, Falini, Brunangelo, von Heydebreck, Anja, Metzler, Dirk, Bräuninger, Andreas, Hansmann, Martin-Leo, Küppers, Ralf
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556780/
https://www.ncbi.nlm.nih.gov/pubmed/18794340
http://dx.doi.org/10.1084/jem.20080809
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author Brune, Verena
Tiacci, Enrico
Pfeil, Ines
Döring, Claudia
Eckerle, Susan
van Noesel, Carel J.M.
Klapper, Wolfram
Falini, Brunangelo
von Heydebreck, Anja
Metzler, Dirk
Bräuninger, Andreas
Hansmann, Martin-Leo
Küppers, Ralf
author_facet Brune, Verena
Tiacci, Enrico
Pfeil, Ines
Döring, Claudia
Eckerle, Susan
van Noesel, Carel J.M.
Klapper, Wolfram
Falini, Brunangelo
von Heydebreck, Anja
Metzler, Dirk
Bräuninger, Andreas
Hansmann, Martin-Leo
Küppers, Ralf
author_sort Brune, Verena
collection PubMed
description The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor κB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
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spelling pubmed-25567802009-03-29 Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis Brune, Verena Tiacci, Enrico Pfeil, Ines Döring, Claudia Eckerle, Susan van Noesel, Carel J.M. Klapper, Wolfram Falini, Brunangelo von Heydebreck, Anja Metzler, Dirk Bräuninger, Andreas Hansmann, Martin-Leo Küppers, Ralf J Exp Med Articles The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor κB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies. The Rockefeller University Press 2008-09-29 /pmc/articles/PMC2556780/ /pubmed/18794340 http://dx.doi.org/10.1084/jem.20080809 Text en © 2008 Brune et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Brune, Verena
Tiacci, Enrico
Pfeil, Ines
Döring, Claudia
Eckerle, Susan
van Noesel, Carel J.M.
Klapper, Wolfram
Falini, Brunangelo
von Heydebreck, Anja
Metzler, Dirk
Bräuninger, Andreas
Hansmann, Martin-Leo
Küppers, Ralf
Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title_full Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title_fullStr Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title_full_unstemmed Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title_short Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
title_sort origin and pathogenesis of nodular lymphocyte–predominant hodgkin lymphoma as revealed by global gene expression analysis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556780/
https://www.ncbi.nlm.nih.gov/pubmed/18794340
http://dx.doi.org/10.1084/jem.20080809
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