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EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
E. Young, D. Noerenberg, L. Mansouri, V. Ljungström, M. Frick, LA. Sutton, SJ. Blakemore, J. Galan-Sousa, K. Plevova, P. Baliakas, D. Rossi, R. Clifford, D. Roos-Weil, V. Navrkalova, B. Dörken, CA. Schmitt, KE. Smedby, G. Juliusson, B....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
NV15-31834A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Zdroj
NLK
ProQuest Central
od 1997-02-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Nursing & Allied Health Database (ProQuest)
od 1997-02-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1997-02-01 do Před 1 rokem
Public Health Database (ProQuest)
od 1997-02-01 do 2017-12-31
PubMed
27890934
DOI
10.1038/leu.2016.359
Knihovny.cz E-zdroje
- MeSH
- chronická lymfatická leukemie klasifikace farmakoterapie genetika mortalita MeSH
- dospělí MeSH
- geny p53 MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- proporcionální rizikové modely MeSH
- protein 2 časné růstové odpovědi genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
1st Department of Propaedeutic Medicine School of Medicine University of Athens Athens Greece
Cancer Sciences Faculty of Medicine University of Southampton Southampton UK
Department of Laboratory Medicine Stem Cell Center Lund University Lund Sweden
Department of Molecular Pathology Royal Bournemouth Hospital Bournemouth UK
Department of Molecular Therapy in Haematology and Oncology Heidelberg Germany
Division of Hematology Department of Internal Medicine The Ohio State University Columbus OH USA
Hematology Department General Hospital of Nikea Piraeus Greece
INSERM U1170 Institut Gustave Roussy Villejuif France
Laboratory of Hematology and Universite Pierre et Marie Curie Hopital Pitie Salpetriere Paris France
Citace poskytuje Crossref.org
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