YOUNG, E., D. NOERENBERG, L. MANSOURI, V. LJUNGSTROM, M. FRICK, L. A. SUTTON, S. J. BLAKEMORE, J. GALAN-SOUSA, Karla PLEVOVÁ, P. BALIAKAS, D. ROSSI, R. CLIFFORD, D. ROOS-WEIL, Veronika NAVRKALOVÁ, B. DOERKEN, C. A. SCHMITT, K. E. SMEDBY, G. JULIUSSON, B. GIACOPELLI, J. S. BLACHLY, C. BELESSI, P. PANAGIOTIDIS, N. CHIORAZZI, F. DAVI, A. W. LANGERAK, D. OSCIER, A. SCHUH, G. GAIDANO, P. GHIA, W. XU, L. FAN, O. A. BERNARD, F. NGUYEN-KHAC, L. RASSENTI, J. LI, T. J. KIPPS, K. STAMATOPOULOS, Šárka POSPÍŠILOVÁ, T. ZENZ, C. C. OAKES, J. C. STREFFORD, R. ROSENQUIST and F. DAMM. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. Leukemia. London: Nature Publishing Group, 2017, vol. 31, No 7, p. 1547-1554. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/leu.2016.359.
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Basic information
Original name EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
Authors YOUNG, E. (752 Sweden), D. NOERENBERG (276 Germany), L. MANSOURI (752 Sweden), V. LJUNGSTROM (752 Sweden), M. FRICK (276 Germany), L. A. SUTTON (752 Sweden), S. J. BLAKEMORE (826 United Kingdom of Great Britain and Northern Ireland), J. GALAN-SOUSA (276 Germany), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), P. BALIAKAS (752 Sweden), D. ROSSI (380 Italy), R. CLIFFORD (826 United Kingdom of Great Britain and Northern Ireland), D. ROOS-WEIL (250 France), Veronika NAVRKALOVÁ (203 Czech Republic, belonging to the institution), B. DOERKEN (276 Germany), C. A. SCHMITT (276 Germany), K. E. SMEDBY (752 Sweden), G. JULIUSSON (752 Sweden), B. GIACOPELLI (840 United States of America), J. S. BLACHLY (840 United States of America), C. BELESSI (300 Greece), P. PANAGIOTIDIS (300 Greece), N. CHIORAZZI (840 United States of America), F. DAVI (250 France), A. W. LANGERAK (528 Netherlands), D. OSCIER (826 United Kingdom of Great Britain and Northern Ireland), A. SCHUH (826 United Kingdom of Great Britain and Northern Ireland), G. GAIDANO (380 Italy), P. GHIA (380 Italy), W. XU (156 China), L. FAN (156 China), O. A. BERNARD (250 France), F. NGUYEN-KHAC (250 France), L. RASSENTI (840 United States of America), J. LI (156 China), T. J. KIPPS (840 United States of America), K. STAMATOPOULOS (752 Sweden), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), T. ZENZ (276 Germany), C. C. OAKES (840 United States of America), J. C. STREFFORD (826 United Kingdom of Great Britain and Northern Ireland), R. ROSENQUIST (752 Sweden) and F. DAMM (276 Germany).
Edition Leukemia, London, Nature Publishing Group, 2017, 0887-6924.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 10.023
RIV identification code RIV/00216224:14740/17:00095650
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1038/leu.2016.359
UT WoS 000404745300009
Keywords in English IDENTIFIES RECURRENT MUTATIONS; LRF CLL4 TRIAL; GENE-MUTATIONS; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTORS; CLONAL EVOLUTION; SF3B1 MUTATIONS; HIGH-THROUGHPUT; ATM MUTATIONS; NOTCH1
Tags MEDGENET, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 28/2/2018 14:37.
Abstract
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.
Links
LQ1601, research and development projectName: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
NV15-31834A, research and development projectName: Vliv selekce genomických poškození na průběh chronické lymfocytární leukémie
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