Differential Eµ enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and Hodgkin lymphomas
| Autor: | Christoph Loddenkemper, Bernd Dörken, Korinna Jöhrens-Leder, Harald Stein, Hans-Dieter Foss, Franziska Jundt, Michael Hummel, Ioannis Anagnostopoulos, Thomas Wirth |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lymphoma
B-Cell Lymphoid Tissue Down-Regulation Immunoglobulins Pathology and Forensic Medicine Transcription (biology) Cell Line Tumor Proto-Oncogene Proteins hemic and lymphatic diseases medicine Centroblasts Humans Enhancer Transcription factor In Situ Hybridization B cell Regulation of gene expression B-Lymphocytes biology Immunoglobulin D medicine.disease Hodgkin Disease Immunohistochemistry Molecular biology Introns Lymphoma Gene Expression Regulation Neoplastic Enhancer Elements Genetic medicine.anatomical_structure Immunoglobulin M Immunology Trans-Activators biology.protein Antibody Octamer Transcription Factor-2 Transcription Factors |
| Zdroj: | The Journal of Pathology. 202:60-69 |
| ISSN: | 1096-9896 0022-3417 |
| Popis: | It has previously been demonstrated that in cultured and in situ tumour cells of classical Hodgkin lymphoma (cHL), the immunoglobulin (Ig) promoter is inactive and its transcription factors Oct2 and/or BOB.1/OBF.1 are down-regulated. In this study, the analysis of these transcription factors has been extended to a broad spectrum of B-cell malignancies and the findings have been related to the situation in normal B-cells of various differentiation stages and to the expression of Ig. Furthermore, an additional Ig transcription factor, PU.1, recently described to be absent from cHL, and a further regulatory element of the Ig gene, the intronic Emu enhancer, have been studied. BOB.1/OBF.1 and Oct2 were present in all B-cells expressing Ig, whereas PU.1 proved to be absent from late B-cell differentiation stages and from a subset of germinal centre B-cells. Interestingly, there were several normal (eg germinal centre centroblasts and monocytoid B-cells) and malignant B-cell populations (eg a proportion of diffuse large B-cell lymphomas, DLBCLs) that were Ig-negative, despite their BOB.1/OBF.1 and Oct2 expression. This study further shows that absence of PU.1 alone, as well as inactivation of the intronic Emu enhancer, is not sufficient to down-regulate Ig transcription. Taken together, the simultaneous absence of PU.1, Oct2, and/or BOB.1/OBF.1 is unique to Hodgkin and Reed-Sternberg (HRS) cells and cannot be detected in normal B-cell subsets or B-cell non-Hodgkin lymphomas (B-NHLs). This supports the concept that the down-regulation of Ig in cHL does not reflect a physiological situation, but a defect probably closely linked to the pathogenesis of cHL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text