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¹ Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany
² Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany
³ Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
⁴ Institute for Pathology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
⁵ Institute of Hematology, University of Perugia, 06100 Perugia, Italy
⁶ Bio- and Chemoinformatics, Merck KGaA, 64293 Darmstadt, Germany
⁷ Institute for Informatics, University of Frankfurt, 60054 Frankfurt, Germany

CORRESPONDENCE Ralf Küppers: ralf.kueppers{at}uk-essen.de

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 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.

M.-L. Hansmann and R. Küppers contributed equally to this paper.

I. Pfeil's present address is Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum, 81377 München, Germany.

© 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/).

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