Activation of the endoplasmic reticulum stress-associated transcription factor X box-binding protein-1 occurs in a subset of normal germinal-center B cells and in aggressive B-cell lymphomas with prognostic implications Journal Article
| Authors: | Balague, O.; Mozos, A.; Martinez, D.; Hernandez, L.; Colomo, L.; Mate, J. L.; Teruya-Feldstein, J.; Lin, O.; Campo, E.; Lopez-Guillermo, A.; Martinez, A. |
| Article Title: | Activation of the endoplasmic reticulum stress-associated transcription factor X box-binding protein-1 occurs in a subset of normal germinal-center B cells and in aggressive B-cell lymphomas with prognostic implications |
| Abstract: | X box-binding protein 1 (Xbp-1) is a transcription factor that is required for the terminal differentiation of B lymphocytes into plasma cells. The Xbp-1 gene is activated in response to endoplasmic reticulum stress signals, which generate a 50-kDa nuclear protein that acts as a potent transactivator and regulates the expression of genes related to the unfolded protein response. Activated Xbp-1 is essential for cell survival in plasma-cell tumors but its role in B-cell lymphomas is unknown. We analyzed the expression of activated Xbp-1 in reactive lymphoid tissues, 411 lymphomas and plasma-cell neoplasms, and 24 B-cell lines. In reactive tissues, Xbp-1 was only found in nuclear extracts. Nuclear expression of Xbp-1 was observed in occasional reactive plasma cells and in a subpopulation of Irf-4<sup>+</sup>/Bcl-6<sup>-</sup>/Pax-5<sup>-</sup> B cells in the light zones of reactive germinal centers, probably representing cells committed to plasma-cell differentiation. None of the low-grade lymphomas showed evidence of Xbp-1 activation; however, Xbp-1 activation was found in 28% of diffuse large B-cell lymphomas, independent of germinal or postgerminal center phenotype, as well as in 48% of plasmablastic lymphomas and 69% of plasma-cell neoplasms. Diffuse large B-cell lymphomas with nuclear Xbp-1 expression had a significantly worse response to therapy and shorter overall survival compared with negative tumors. These findings suggest that Xbp-1 activation may play a role in the pathogenesis of aggressive B-cell lymphomas. Copyright © American Society for Investigative Pathology. |
| Keywords: | immunohistochemistry; adult; human tissue; middle aged; major clinical study; dna-binding proteins; prednisone; doxorubicin; protein function; phenotype; gene; cell survival; x box binding protein 1; microscopy, confocal; cyclophosphamide; plasmacytoma; cell differentiation; enzyme activation; b lymphocyte; b-lymphocytes; transcription factors; prednisolone; vincristine sulfate; b cell lymphoma; gene activation; germinal center; lymphocyte differentiation; plasma cell; xbp 1 gene; blotting, western; endoplasmic reticulum; fluorescent antibody technique; gene expression regulation, neoplastic; lymphoma, b-cell |
| Journal Title: | American Journal of Pathology |
| Volume: | 174 |
| Issue: | 6 |
| ISSN: | 0002-9440 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2009-06-01 |
| Start Page: | 2337 |
| End Page: | 2346 |
| Language: | English |
| DOI: | 10.2353/ajpath.2009.080848 |
| PUBMED: | 19389935 |
| PROVIDER: | scopus |
| PMCID: | PMC2684197 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: AJPAA" - "Source: Scopus" |
Altmetric
Citation Impact
Related MSK Work