| Title | Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. | | Author(s) | Schwering I, Bräuninger A, Klein U, Jungnickel B, Tinguely M, Diehl V, Hansmann ML, Dalla-Favera R, Rajewsky K, Küppers R | | Institution | Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany. ines.schwering@medizin.uni-koeln.de | | Source | Blood 2003 Feb 15; 101(4):1505-12. | | MeSH | B-Cell-Specific Activator Protein
B-Lymphocytes
Biological Markers
Cell Differentiation
DNA-Binding Proteins
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hodgkin Disease
Humans
Immunohistochemistry
Lymph Nodes
Mutation
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Receptors, Antigen, B-Cell
Reed-Sternberg Cells
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription Factors
Tumor Cells, Cultured
| | Abstract | Hodgkin and Reed-Sternberg (HRS) cells represent the malignant cells in classical Hodgkin lymphoma (HL). Because their immunophenotype cannot be attributed to any normal cell of the hematopoietic lineage, the origin of HRS cells has been controversially discussed, but molecular studies established their derivation from germinal center B cells. In this study, gene expression profiles generated by serial analysis of gene expression (SAGE) and DNA chip microarrays from HL cell lines were compared with those of normal B-cell subsets, focusing here on the expression of B-lineage markers. This analysis revealed decreased mRNA levels for nearly all established B-lineage-specific genes. For 9 of these genes, lack of protein expression was histochemically confirmed. Down-regulation of genes affected multiple components of signaling pathways active in B cells, including B-cell receptor (BCR) signaling. Because several genes down-regulated in HRS cells are positively regulated by the transcriptional activator Pax-5, which is expressed in most HRS cells, we studied HL cell lines for mutations in the Pax-5 gene. However, no mutations were found. We propose that the lost B-lineage identity in HRS cells may explain their survival without BCR expression and reflect a fundamental defect in maintaining the B-cell differentiation state in HRS cells, which is likely caused by a novel, yet unknown, pathogenic mechanism. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12393731 |
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