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Frequent NFKBIE del...
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Mansouri, LarryUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist
(author)
Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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American Society of Hematology,2016
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-314939
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-314939URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-131885URI
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https://doi.org/10.1182/blood-2016-03-704528DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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L.M., D.N., and E.Y. contributed equally to this study as joint first authors.R.R. and F.D. contributed equally as joint senior authors.
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We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIEaberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Noerenberg, DanielDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Young, Emma,1990-Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell(Swepub:uu)emmyo327
(author)
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Mylonas, ElenaDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Abdulla, MaysaaUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Rose-Marie Amini(Swepub:uu)mayab806
(author)
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Frick, MareikeDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Asmar, FazilaDepartment of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
(author)
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Ljungström, ViktorUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)viklj600
(author)
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Schneider, MarkusInstitute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
(author)
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Yoshida, KenichiDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
(author)
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Skaftason, AronUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)arosk159
(author)
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Pandzic, TatjanaUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)tatdj291
(author)
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Gonzalez, BlancaDepartment of Pathology, Hospital Clinic and Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
(author)
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Tasidou, AnnaHematopathology Department, Evangelismos Hospital, Athens, Greece
(author)
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Waldhueter, NilsDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Rivas-Delgado, AlfredoHematology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
(author)
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Angelopoulou, MariaDepartment of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
(author)
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Ziepert, MaritaInstitute for Medical Informatics, Statistics, and Epidemiology, University at Leipzig, Leipzig, Germany
(author)
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Arends, Christopher-MaximilianDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Couronne, LucileService d’Hematologie Adulte, Assistance Publique–Hopitaux de Paris, Hopital Necker, Paris, France
(author)
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Lenze, DidoInstitute of Pathology, Charite University Medical Center, Berlin, Germany
(author)
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Claudia, BaldusDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Bastard, ChristianINSERM U918, Universite de Rouen, Centre Henri Becquerel, Rouen, France
(author)
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Okosun, JessicaCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
(author)
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Fitzgibbon, JudeCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
(author)
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Dörken, BerndDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Drexler, Hans GLeibniz-Institute DSMZ–German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
(author)
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Roos-Weil, DamienUniversity Paris-Sud, Orsay, France, INSERM, U1170, Institut Gustave Roussy, Villejuif, France and Equipe Labellisee Ligue Nationale Contre le Cancer, Paris, France
(author)
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Schmitt, Clemens ADepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
(author)
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Munch-Petersen, Helga DDepartment of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
(author)
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Zenz, ThorstenDepartments of Molecular Therapy in Haematology and Oncology and Translational Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany, Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany and German Consortium for Translational Cancer Research, Heidelberg, Germany
(author)
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Hansmann, Martin-LeoDr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany
(author)
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Strefford, Jonathan CAcademic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
(author)
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Enblad, GunillaUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)gunienbl
(author)
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Bernard, OlivierUniversity Paris-Sud, Orsay, France, INSERM, U1170, Institut Gustave Roussy, Villejuif, France and Equipe Labellisee Ligue Nationale Contre le Cancer, Paris, France
(author)
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Ralfkiaer, ElisabethDepartment of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
(author)
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Erlanson, MartinUmeå universitet,Onkologi,Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden(Swepub:umu)maer0058
(author)
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Korkolopoulou, PenelopeDepartment of Pathology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
(author)
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Hultdin, MagnusUmeå universitet,Patologi,Department of Medical Biosciences, Pathology, Umeå University, Umeå Sweden(Swepub:umu)magn0001
(author)
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Papadaki, TheodoraHematopathology Department, Evangelismos Hospital, Athens, Greece,Department of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
(author)
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Grønbæk, KirstenDepartment of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
(author)
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Lopez-Guillermo, ArmandoHematology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
(author)
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Ogawa, SeishiDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
(author)
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Küppers, RalfInstitute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
(author)
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Stamatopoulos, KostasUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece(Swepub:uu)kosst292
(author)
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Stavroyianni, NikiHematology Department and Hematopoietic Cell Transplantation Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
(author)
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Kanellis, GeorgeHematopathology Department, Evangelismos Hospital, Athens, Greece
(author)
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Rosenwald, AndreasInstitute of Pathology, University of Würzburg, Würzburg, Germany and Comprehensive Cancer Center Mainfranken, Würzburg, Germany
(author)
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Campo, EliasDepartment of Pathology, Hospital Clinic and Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
(author)
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Amini, Rose-MarieUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Rose-Marie Amini(Swepub:uu)roseamin
(author)
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Ott, GermanDepartment of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
(author)
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Vasslakopoulos, Theodoros PDepartment of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
(author)
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Hummel, MichaelInstitute of Pathology, Charite University Medical Center, Berlin, Germany
(author)
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Rosenquist, RichardUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)richrose
(author)
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Damm, FrederikDepartment of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany and Berlin Institute of Health, Berlin, Germany
(author)
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Gronbaek, Kirsten
(author)
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Uppsala universitetExperimentell och klinisk onkologi
(creator_code:org_t)
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In:Blood: American Society of Hematology128:23, s. 2666-26700006-49711528-0020
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Asmar, Fazila
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Angelopoulou, Ma ...
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