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 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.
Brune
Verena
V
Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany.
Tiacci
Enrico
E
Pfeil
Ines
I
Döring
Claudia
C
Eckerle
Susan
S
van Noesel
Carel J M
CJ
Klapper
Wolfram
W
Falini
Brunangelo
B
von Heydebreck
Anja
A
Metzler
Dirk
D
Bräuninger
Andreas
A
Hansmann
Martin-Leo
ML
Küppers
Ralf
R
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
D015415:Biomarkers; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases
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