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Sökning: WFRF:(Blakemore A.) > EGR2 mutations defi...

  • Young, Emma,1990-Uppsala universitet,Experimentell och klinisk onkologi,Richard Rosenquist Brandell (författare)

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • 2016-11-28
  • Springer Science and Business Media LLC,2017
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-314928
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-314928URI
  • https://doi.org/10.1038/leu.2016.359DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:136136922URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • E.Y. and D.N. contributed equally to this study as joint first authors.R.R. and F.D. contributed equally as joint senior authors.
  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Noerenberg, DanielDepartment of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany (författare)
  • Mansouri, LarryUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell(Swepub:uu)maman377 (författare)
  • Ljungström, Viktor,1986-Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell(Swepub:uu)viklj600 (författare)
  • Frick, MareikeDepartment of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany (författare)
  • Sutton, Lesley AnnKarolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist(Swepub:uu)lessu455 (författare)
  • Blakemore, Stuart JamesCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK (författare)
  • Galan-Sousa, JoelDepartment of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany (författare)
  • Plevova, KarlaCentral European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic (författare)
  • Baliakas, Panagiotis,1977-Uppsala universitet,Science for Life Laboratory, SciLifeLab(Swepub:uu)panba345 (författare)
  • Rossi, DavideDivision 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 (författare)
  • Ruth, CliffordOxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK (författare)
  • Roos-Weil, DamienINSERM, U1170, Institut Gustave Roussy, Villejuif, France (författare)
  • Navrklova, VeronikaEuropean Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic (författare)
  • Dörken, BerndDepartment of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany (författare)
  • Schmitt, Clemens ADepartment of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany (författare)
  • Ekström Smedby, KarinKarolinska Institutet (författare)
  • Juliusson, GunnarDepartment of Laboratory Medicine, Stem Cell Center, Lund University, Lund, Sweden (författare)
  • Giacopelli, BrianDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA (författare)
  • Blachly, JamesDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA (författare)
  • Belessi, ChrysoulaHematology Department, General Hospital of Nikea, Piraeus, Greece (författare)
  • Panayiotidis, PanayiotisFirst Department of Propaedeutic Medicine, School of Medicine, University of Athens, Athens, Greece (författare)
  • Chiorazzi, NicholasKarches Center for Chronic Lymphocytic Leukemia Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA (författare)
  • Davi, FrédéricLaboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France (författare)
  • Langerak, Anton WDepartment of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (författare)
  • Oscier, DavidDepartment of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK (författare)
  • Schuh, AnnaOxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK (författare)
  • Gaidano, GianlucaDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy (författare)
  • Ghia, PaoloUniversità 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 (författare)
  • Xu, WeiDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China (författare)
  • Fan, LeiDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China (författare)
  • Bernard, Olivier AINSERM, U1170, Institut Gustave Roussy, Villejuif, France (författare)
  • Nguyen-Khac, FlorenceLaboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France (författare)
  • Rassenti, Laura ZDivision of Hematology/Oncology, Department of Medicine, University of California at San Diego/Moores Cancer Center, La Jolla, CA, USA (författare)
  • Li, JianyonglmDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China (författare)
  • Kipps, Thomas JDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA (författare)
  • Stamatopoulos, KostasUppsala 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(Swepub:uu)kosst292 (författare)
  • Pospisilova, SarkaCentral European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic (författare)
  • Zenz, ThorstenDepartment 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 (författare)
  • Strefford, JonathanCancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK (författare)
  • Rosenquist, RichardKarolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell(Swepub:uu)richrose (författare)
  • Damm, FrederikDepartment 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 (författare)
  • Oakes, CC (författare)
  • Uppsala universitetExperimentell och klinisk onkologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Leukemia: Springer Science and Business Media LLC31:7, s. 1547-15540887-69241476-5551

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  • Leukemia (Sök värdpublikationen i LIBRIS)

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