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dc.contributor.author | Wong, Kah Keng | |
dc.contributor.author | Gascoyne, Duncan M | |
dc.contributor.author | Soilleux, Elizabeth J | |
dc.contributor.author | Lyne, Linden | |
dc.contributor.author | Spearman, Hayley | |
dc.contributor.author | Roncador, Giovanna | |
dc.contributor.author | Pedersen, Lars M | |
dc.contributor.author | Møller, Michael B | |
dc.contributor.author | Green, Tina M | |
dc.contributor.author | Banham, Alison H | |
dc.date.accessioned | 2020-07-13T16:22:45Z | |
dc.date.available | 2020-07-13T16:22:45Z | |
dc.date.issued | 2016-08-16 | |
dc.identifier.citation | Oncotarget . 2016 ;7(33):52940-52956. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10750 | |
dc.description.abstract | FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Impact Journals | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | TRANSCRIPTION FACTOR FOXP2; | es_ES |
dc.subject | CLASS-II EXPRESSION | es_ES |
dc.subject | NF-KAPPA-B | es_ES |
dc.subject | DOWN-REGULATION | es_ES |
dc.subject | PROTEIN HIP1R | es_ES |
dc.subject | GENE | es_ES |
dc.subject | SURVIVAL | es_ES |
dc.subject | BLIMP-1 | es_ES |
dc.subject | DIFFERENTIATION | es_ES |
dc.subject | LYMPHOCYTES | es_ES |
dc.subject.mesh | Adult | es_ES |
dc.subject.mesh | Aged | es_ES |
dc.subject.mesh | Aged, 80 and over | es_ES |
dc.subject.mesh | Antibodies, Monoclonal, Murine-Derived | es_ES |
dc.subject.mesh | Antineoplastic Combined Chemotherapy Protocols | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Cyclophosphamide | es_ES |
dc.subject.mesh | Doxorubicin | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Forkhead Transcription Factors | es_ES |
dc.subject.mesh | Gene Expression Profiling | es_ES |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | es_ES |
dc.subject.mesh | Gene Ontology | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Kaplan-Meier Estimate | es_ES |
dc.subject.mesh | Lymphoma, Large B-Cell, Diffuse | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Middle Aged | es_ES |
dc.subject.mesh | Prednisone | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | Repressor Proteins | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Transcriptome | es_ES |
dc.subject.mesh | Vincristine | es_ES |
dc.subject.mesh | Young Adult | es_ES |
dc.title | FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 27224915 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 33 | es_ES |
dc.format.page | 52940-52956 | es_ES |
dc.identifier.doi | 10.18632/oncotarget.9507 | es_ES |
dc.contributor.funder | Universiti Sains Malaysia (Malasia) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1949-2553 | es_ES |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.9507 | es_ES |
dc.identifier.journal | Oncotarget | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Unidades técnicas::Unidad de Anticuerpos Monoclonales | es_ES |
dc.rights.accessRights | open access | es_ES |