TY - JOUR
T1 - Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis
AU - Brune, Verena
AU - Tiacci, Enrico
AU - Pfeil, Ines
AU - Doering, Claudia
AU - Eckerle, Susan
AU - van Noesel, Carel J. M.
AU - Klapper, Wolfram
AU - Falini, Brunangelo
AU - von Heydebreck, Anja
AU - Metzler, Dirk
AU - Braeuninger, Andreas
AU - Hansmann, Martin-Leo
AU - Kueppers, Ralf
PY - 2008
Y1 - 2008
N2 - 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 kappa 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
AB - 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 kappa 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
U2 - https://doi.org/10.1084/jem.20080809
DO - https://doi.org/10.1084/jem.20080809
M3 - Article
C2 - 18794340
SN - 0022-1007
VL - 205
SP - 2251
EP - 2268
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -