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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.

SUBMITTER: Brune V 

PROVIDER: S-EPMC2556780 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Brune Verena V   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  

The Journal of experimental medicine 20080915 10


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  ...[more]

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