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Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma

Mansouri, Larry (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist
Noerenberg, Daniel (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Young, Emma, 1990- (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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Mylonas, Elena (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Abdulla, Maysaa (author)
Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Rose-Marie Amini
Frick, Mareike (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Asmar, Fazila (author)
Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Ljungström, Viktor (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
Schneider, Markus (author)
Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
Yoshida, Kenichi (author)
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Skaftason, Aron (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
Pandzic, Tatjana (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
Gonzalez, Blanca (author)
Department of Pathology, Hospital Clinic and Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
Tasidou, Anna (author)
Hematopathology Department, Evangelismos Hospital, Athens, Greece
Waldhueter, Nils (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Rivas-Delgado, Alfredo (author)
Hematology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
Angelopoulou, Maria (author)
Department of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
Ziepert, Marita (author)
Institute for Medical Informatics, Statistics, and Epidemiology, University at Leipzig, Leipzig, Germany
Arends, Christopher-Maximilian (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Couronne, Lucile (author)
Service d’Hematologie Adulte, Assistance Publique–Hopitaux de Paris, Hopital Necker, Paris, France
Lenze, Dido (author)
Institute of Pathology, Charite University Medical Center, Berlin, Germany
Claudia, Baldus (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Bastard, Christian (author)
INSERM U918, Universite de Rouen, Centre Henri Becquerel, Rouen, France
Okosun, Jessica (author)
Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
Fitzgibbon, Jude (author)
Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
Dörken, Bernd (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Drexler, Hans G (author)
Leibniz-Institute DSMZ–German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
Roos-Weil, Damien (author)
University Paris-Sud, Orsay, France, INSERM, U1170, Institut Gustave Roussy, Villejuif, France and Equipe Labellisee Ligue Nationale Contre le Cancer, Paris, France
Schmitt, Clemens A (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany
Munch-Petersen, Helga D (author)
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Zenz, Thorsten (author)
Departments 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
Hansmann, Martin-Leo (author)
Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany
Strefford, Jonathan C (author)
Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
Enblad, Gunilla (author)
Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab
Bernard, Olivier (author)
University Paris-Sud, Orsay, France, INSERM, U1170, Institut Gustave Roussy, Villejuif, France and Equipe Labellisee Ligue Nationale Contre le Cancer, Paris, France
Ralfkiaer, Elisabeth (author)
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Erlanson, Martin (author)
Umeå universitet,Onkologi,Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
Korkolopoulou, Penelope (author)
Department of Pathology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
Hultdin, Magnus (author)
Umeå universitet,Patologi,Department of Medical Biosciences, Pathology, Umeå University, Umeå Sweden
Papadaki, Theodora (author)
Hematopathology Department, Evangelismos Hospital, Athens, Greece,Department of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
Grønbæk, Kirsten (author)
Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Lopez-Guillermo, Armando (author)
Hematology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
Ogawa, Seishi (author)
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Küppers, Ralf (author)
Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
Stamatopoulos, Kostas (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
Stavroyianni, Niki (author)
Hematology Department and Hematopoietic Cell Transplantation Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
Kanellis, George (author)
Hematopathology Department, Evangelismos Hospital, Athens, Greece
Rosenwald, Andreas (author)
Institute of Pathology, University of Würzburg, Würzburg, Germany and Comprehensive Cancer Center Mainfranken, Würzburg, Germany
Campo, Elias (author)
Department of Pathology, Hospital Clinic and Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
Amini, Rose-Marie (author)
Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Rose-Marie Amini
Ott, German (author)
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
Vasslakopoulos, Theodoros P (author)
Department of Haematology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
Hummel, Michael (author)
Institute of Pathology, Charite University Medical Center, Berlin, Germany
Rosenquist, Richard (author)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
Damm, Frederik (author)
Department of Hematology, Oncology, and Tumor Immunology, Charite, University Medical Center, Berlin, Germany and Berlin Institute of Health, Berlin, Germany
Gronbaek, Kirsten (author)
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 (creator_code:org_t)
American Society of Hematology, 2016
2016
English.
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. 2666-2670
  • Journal article (peer-reviewed)
Abstract Subject headings
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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

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Molekylär genetik
Molecular Genetics
Pathology
Patologi

Publication and Content Type

ref (subject category)
art (subject category)

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Mansouri, Larry
Noerenberg, Dani ...
Young, Emma, 199 ...
Mylonas, Elena
Abdulla, Maysaa
Frick, Mareike
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Asmar, Fazila
Ljungström, Vikt ...
Schneider, Marku ...
Yoshida, Kenichi
Skaftason, Aron
Pandzic, Tatjana
Gonzalez, Blanca
Tasidou, Anna
Waldhueter, Nils
Rivas-Delgado, A ...
Angelopoulou, Ma ...
Ziepert, Marita
Arends, Christop ...
Couronne, Lucile
Lenze, Dido
Claudia, Baldus
Bastard, Christi ...
Okosun, Jessica
Fitzgibbon, Jude
Dörken, Bernd
Drexler, Hans G
Roos-Weil, Damie ...
Schmitt, Clemens ...
Munch-Petersen, ...
Zenz, Thorsten
Hansmann, Martin ...
Strefford, Jonat ...
Enblad, Gunilla
Bernard, Olivier
Ralfkiaer, Elisa ...
Erlanson, Martin
Korkolopoulou, P ...
Hultdin, Magnus
Papadaki, Theodo ...
Grønbæk, Kirsten
Lopez-Guillermo, ...
Ogawa, Seishi
Küppers, Ralf
Stamatopoulos, K ...
Stavroyianni, Ni ...
Kanellis, George
Rosenwald, Andre ...
Campo, Elias
Amini, Rose-Mari ...
Ott, German
Vasslakopoulos, ...
Hummel, Michael
Rosenquist, Rich ...
Damm, Frederik
Gronbaek, Kirste ...
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Hematology
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Clinical Laborat ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
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Blood
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Uppsala University
Umeå University

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