Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma.
Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (HL) and lymphocytic and histiocytic (L&H) cells in nodular lymphocyte-predominant HL (NLPHL) are derived from germinal-center B cells. HRS cells have, however, largely lost their B cell phenotype and aberrantly express markers and transcriptional regulators of other hematolymphoid cell types. Deregulation of multiple signaling pathways and downstream transcription factors, including receptor tyrosine kinases, nuclear factor-kappa B (NF-kappaB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), is a further hallmark of HRS cells. These cells harbor genetic lesions that contribute to or cause increases in the activity of transcription factors of the NF-kappaB and STAT families. HRS cells are found within a mixed reactive cellular infiltrate and interact with these nonmalignant cells in a complex fashion that appears to be essential for HRS cell survival and proliferation. Less is known about the pathogenesis of L&H cells in NLPHL, but increases in the activity of receptor tyrosine kinases, NF-kappaB, and JAK/STAT have also been detected.
Schmitz
Roland
R
Institute for Cell Biology (Tumor Research), Medical School, University of Duisburg-Essen, Essen, Germany. roland.schmitz@uni-duisburg-essen.de
Stanelle
Jens
J
Hansmann
Martin-Leo
ML
Küppers
Ralf
R
D002454:Cell Differentiation; D019070:Cell Lineage; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006644:Histiocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000473:pathology; D008479:Mediastinal Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D016328:NF-kappa B; D050791:STAT Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D053612:Janus Kinases