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 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 {kappa}B 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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Author:Verena Brune, Enrico Tiacci, Ines Pfeil, Claudia DöringGND, Susan Eckerle, Carel J. M. van Noesel, Wolfram Klapper, Brunangelo Falini, Anja von Heydebreck, Dirk MetzlerORCiDGND, Andreas Bräuninger, Martin-Leo HansmannGND, Ralf KüppersORCiDGND
Parent Title (German):The Journal of Experimental Medicine
Document Type:Article
Date of Publication (online):2009/09/07
Date of first Publication:2008/09/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/09/07
First Page:2251
Last Page:2268
© 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/).
Source:The Journal of Experimental Medicine, Vol. 205, No. 10, 2251-2268 ; doi:10.1084/jem.20080809 ; http://www.jem.org/cgi/doi/10.1084/jem.20080809 ; Published online September 15, 2008
Institutes:Informatik und Mathematik / Informatik
Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoDeutsches Urheberrecht