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Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma
Author(s) -
Bräuninger Andreas,
Schmitz Roland,
Bechtel Dörte,
Renné Christoph,
Hansmann MartinLeo,
Küppers Ralf
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21716
Subject(s) - reed–sternberg cell , germinal center , biology , lymphoma , somatic hypermutation , cancer research , b cell , b cell receptor , breakpoint cluster region , epstein–barr virus , gene , microbiology and biotechnology , virus , antibody , virology , genetics , immunology , hodgkin lymphoma
Hodgkin's and Reed/Sternberg (HRS) cells, the tumour cells in classical Hodgkin's lymphoma (HL), represent transformed B cells in nearly all cases. The detection of destructive somatic mutations in the rearranged immunoglobulin (Ig) genes of HRS cells in classical HL indicated that they originate from preapoptotic germinal centre (GC) B cells that lost the capacity to express a high‐affinity B‐cell receptor (BCR). Several aberrantly activated signalling pathways and transcription factors have been identified that contribute to the rescue of HRS cells from apoptosis. Among the deregulated signalling pathways, activation of multiple receptor tyrosine kinases in HRS cells appears to be a specific feature of HL. In about 40% of cases of classical HL the HRS cells are infected by Epstein‐Barr virus (EBV), indicating an important role of EBV in HL pathogenesis. Interestingly, nearly all cases of HL with destructive Ig gene mutations eliminating BCR expression (e.g. nonsense mutations) are EBV‐positive, suggesting that EBV‐encoded genes have a particular function to prevent apoptosis of HRS‐cell precursors that acquired such crippling mutations. This idea is further supported by the recent demonstration that isolated human GC B cells harbouring crippled Ig genes can be rescued by EBV from cell death, giving rise to lymphoblastoid cell lines. The molecular analysis of composite Hodgkin's and non‐Hodgkin's lymphomas indicated that many cases develop from a common GC B‐cell precursor in a multistep transformation process with both shared and distinct oncogenic events. © 2005 Wiley‐Liss, Inc.