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

نویسندگان

  • Verena Brune
  • Enrico Tiacci
  • Ines Pfeil
  • Claudia Döring
  • Susan Eckerle
  • Carel J.M. van Noesel
  • Wolfram Klapper
  • Brunangelo Falini
  • Anja von Heydebreck
  • Dirk Metzler
  • Andreas Bräuninger
  • Martin-Leo Hansmann
  • Ralf Küppers
چکیده

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.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 205  شماره 

صفحات  -

تاریخ انتشار 2008