Molecular biology of Hodgkin lymphoma.
Hodgkin lymphoma (HL) is derived from mature B cells and subdivided into classical HL and nodular lymphocyte predominant HL (NLPHL). HL is unique among human B cell lymphomas because of the rarity of the lymphoma cells, the Hodgkin and Reed-Sternberg (HRS) cells in classical HL and the lymphocyte-predominant (LP) cells in NLPHL, which usually account for 0.1% to 10% of the cells in the affected tissues. Moreover, HRS cells are unique in the extent to which they have lost their B cell-typical gene expression pattern. Deregulation of transcription factor networks plays a key role in this reprogramming process. HRS cells show strong constitutive activity of the transcription factor NF-kappaB. Multiple mechanisms likely contribute to this deregulated activation, including signaling through particular receptors and genetic lesions. Inactivating mutations in the TNFAIP3 tumor suppressor gene, encoding a negative regulator of NF-kappaB activity, were recently identified in about 40% of patients with classical HL. HRS cells are latently infected by Epstein-Barr virus in about 40% of patients, and an important role of this virus in HL pathogenesis-in particular for cases in which HRS cells had lost the capacity to express a B-cell receptor due to destructive somatic mutation-was recently substantiated.
Küppers
Ralf
R
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany. ralf.kueppers@uk-essen.de
D001402:B-Lymphocytes / Q000473:pathology* / Q000821:virology; D054337:Cell Dedifferentiation; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000473:pathology / Q000821:virology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3