title: Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis.
abstract: 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 kappaB 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.
authors.affiliation: Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Brune
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiacci
authors.forename: Ines
authors.initials: I
authors.lastname: Pfeil
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.forename: Susan
authors.initials: S
authors.lastname: Eckerle
authors.forename: Carel J M
authors.initials: CJ
authors.lastname: van Noesel
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Anja
authors.initials: A
authors.lastname: von Heydebreck
authors.forename: Dirk
authors.initials: D
authors.lastname: Metzler
authors.forename: Andreas
authors.initials: A
authors.lastname: Bräuninger
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D003937:Diagnosis, Differential; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000166:cytology; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000235:genetics / Q000276:immunology / Q000473:pathology; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases
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