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EGR2 mutations defi...
EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
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- Young, Emma, 1990- (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Richard Rosenquist Brandell
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- Noerenberg, Daniel (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany
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- Mansouri, Larry (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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- Ljungström, Viktor, 1986- (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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- Frick, Mareike (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany
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- Sutton, Lesley Ann (author)
- Karolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist
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- Blakemore, Stuart James (author)
- Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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- Galan-Sousa, Joel (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany
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- Plevova, Karla (author)
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic
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- Baliakas, Panagiotis, 1977- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Rossi, Davide (author)
- Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy and Hematology, Oncology Institute of Southern Switzerland and Institute of Oncology Research, Bellinzona, Switzerland
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- Ruth, Clifford (author)
- Oxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK
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- Roos-Weil, Damien (author)
- INSERM, U1170, Institut Gustave Roussy, Villejuif, France
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- Navrklova, Veronika (author)
- European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic
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- Dörken, Bernd (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany
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- Schmitt, Clemens A (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany
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- Ekström Smedby, Karin (author)
- Karolinska Institutet
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- Juliusson, Gunnar (author)
- Department of Laboratory Medicine, Stem Cell Center, Lund University, Lund, Sweden
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- Giacopelli, Brian (author)
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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- Blachly, James (author)
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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- Belessi, Chrysoula (author)
- Hematology Department, General Hospital of Nikea, Piraeus, Greece
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- Panayiotidis, Panayiotis (author)
- First Department of Propaedeutic Medicine, School of Medicine, University of Athens, Athens, Greece
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- Chiorazzi, Nicholas (author)
- Karches Center for Chronic Lymphocytic Leukemia Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA
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- Davi, Frédéric (author)
- Laboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
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- Langerak, Anton W (author)
- Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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- Oscier, David (author)
- Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK
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- Schuh, Anna (author)
- Oxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK
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- Gaidano, Gianluca (author)
- Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
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- Ghia, Paolo (author)
- Università Vita-Salute San Raffaele, Milan, Italy and Division of Experimental Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy
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- Xu, Wei (author)
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China
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- Fan, Lei (author)
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China
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- Bernard, Olivier A (author)
- INSERM, U1170, Institut Gustave Roussy, Villejuif, France
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- Nguyen-Khac, Florence (author)
- Laboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
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- Rassenti, Laura Z (author)
- Division of Hematology/Oncology, Department of Medicine, University of California at San Diego/Moores Cancer Center, La Jolla, CA, USA
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- Li, Jianyonglm (author)
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China
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- Kipps, Thomas J (author)
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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- Stamatopoulos, Kostas (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Sweden and Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
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- Pospisilova, Sarka (author)
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic
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- Zenz, Thorsten (author)
- Department of Molecular Therapy in Haematology and Oncology (G250) and Department of Translational Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
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- Strefford, Jonathan (author)
- Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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- Rosenquist, Richard (author)
- Karolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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- Damm, Frederik (author)
- Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany; German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany and Berlin Institute of Health (BIH), Berlin, Germany
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Oakes, CC (author)
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(creator_code:org_t)
- 2016-11-28
- 2017
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:7, s. 1547-1554
- Related links:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n = 1283) and two validation cohorts (UK CLL4 trial patients, n = 366; CLL Research Consortium (CRC) patients, n = 490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2- mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Oncology
- Onkologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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Leukemia
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Young, Emma, 199 ...
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Noerenberg, Dani ...
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Mansouri, Larry
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Ljungström, Vikt ...
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Frick, Mareike
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Sutton, Lesley A ...
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Blakemore, Stuar ...
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Galan-Sousa, Joe ...
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Plevova, Karla
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Baliakas, Panagi ...
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Rossi, Davide
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Ruth, Clifford
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Roos-Weil, Damie ...
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Navrklova, Veron ...
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Dörken, Bernd
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Schmitt, Clemens ...
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Ekström Smedby, ...
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Juliusson, Gunna ...
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Giacopelli, Bria ...
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Blachly, James
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Belessi, Chrysou ...
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Panayiotidis, Pa ...
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Chiorazzi, Nicho ...
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Davi, Frédéric
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Langerak, Anton ...
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Oscier, David
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Schuh, Anna
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Gaidano, Gianluc ...
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Ghia, Paolo
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Xu, Wei
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Fan, Lei
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Bernard, Olivier ...
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Nguyen-Khac, Flo ...
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Rassenti, Laura ...
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Li, Jianyonglm
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Kipps, Thomas J
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Stamatopoulos, K ...
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Pospisilova, Sar ...
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Zenz, Thorsten
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Strefford, Jonat ...
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Rosenquist, Rich ...
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Damm, Frederik
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Oakes, CC
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Leukemia
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Uppsala University
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Karolinska Institutet