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

J 2017

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

YOUNG, E.; D. NOERENBERG; L. MANSOURI; V. LJUNGSTROM; M. FRICK et al.

Základní údaje

Originální název

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

Autoři

Vydání

Leukemia, London, Nature Publishing Group, 2017, 0887-6924

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 10.023

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00095650

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

IDENTIFIES RECURRENT MUTATIONS; LRF CLL4 TRIAL; GENE-MUTATIONS; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTORS; CLONAL EVOLUTION; SF3B1 MUTATIONS; HIGH-THROUGHPUT; ATM MUTATIONS; NOTCH1

Štítky

MEDGENET, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 2. 2018 14:37, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

NV15-31834A, projekt VaV

Název: Vliv selekce genomických poškození na průběh chronické lymfocytární leukémie

Citovat

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 a F. DAMM. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. Leukemia. London: Nature Publishing Group, 2017, roč. 31, č. 7, s. 1547-1554. ISSN 0887-6924. Dostupné z: https://doi.org/10.1038/leu.2016.359.

@article{1386746,
   author = {Young, E. and Noerenberg, D. and Mansouri, L. and Ljungstrom, V. and Frick, M. and Sutton, L. A. and Blakemore, S. J. and GalanandSousa, J. and Plevová, Karla and Baliakas, P. and Rossi, D. and Clifford, R. and RoosandWeil, D. and Navrkalová, Veronika and Doerken, B. and Schmitt, C. A. and Smedby, K. E. and Juliusson, G. and Giacopelli, B. and Blachly, J. S. and Belessi, C. and Panagiotidis, P. and Chiorazzi, N. and Davi, F. and Langerak, A. W. and Oscier, D. and Schuh, A. and Gaidano, G. and Ghia, P. and Xu, W. and Fan, L. and Bernard, O. A. and NguyenandKhac, F. and Rassenti, L. and Li, J. and Kipps, T. J. and Stamatopoulos, K. and Pospíšilová, Šárka and Zenz, T. and Oakes, C. C. and Strefford, J. C. and Rosenquist, R. and Damm, F.},
   article_location = {London},
   article_number = {7},
   doi = {https://doi.org/10.1038/leu.2016.359},
   keywords = {IDENTIFIES RECURRENT MUTATIONS; LRF CLL4 TRIAL; GENE-MUTATIONS; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTORS; CLONAL EVOLUTION; SF3B1 MUTATIONS; HIGH-THROUGHPUT; ATM MUTATIONS; NOTCH1},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia},
   url = {http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true},
   volume = {31},
   year = {2017}
}

TY  - JOUR
ID  - 1386746
AU  - Young, E. - Noerenberg, D. - Mansouri, L. - Ljungstrom, V. - Frick, M. - Sutton, L. A. - Blakemore, S. J. - Galan-Sousa, J. - Plevová, Karla - Baliakas, P. - Rossi, D. - Clifford, R. - Roos-Weil, D. - Navrkalová, Veronika - Doerken, B. - Schmitt, C. A. - Smedby, K. E. - Juliusson, G. - Giacopelli, B. - Blachly, J. S. - Belessi, C. - Panagiotidis, P. - Chiorazzi, N. - Davi, F. - Langerak, A. W. - Oscier, D. - Schuh, A. - Gaidano, G. - Ghia, P. - Xu, W. - Fan, L. - Bernard, O. A. - Nguyen-Khac, F. - Rassenti, L. - Li, J. - Kipps, T. J. - Stamatopoulos, K. - Pospíšilová, Šárka - Zenz, T. - Oakes, C. C. - Strefford, J. C. - Rosenquist, R. - Damm, F.
PY  - 2017
TI  - EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
JF  - Leukemia
VL  - 31
IS  - 7
SP  - 1547-1554
EP  - 1547-1554
PB  - Nature Publishing Group
SN  - 08876924
KW  - IDENTIFIES RECURRENT MUTATIONS
KW  - LRF CLL4 TRIAL
KW  - GENE-MUTATIONS
KW  - MYELODYSPLASTIC SYNDROMES
KW  - TRANSCRIPTION FACTORS
KW  - CLONAL EVOLUTION
KW  - SF3B1 MUTATIONS
KW  - HIGH-THROUGHPUT
KW  - ATM MUTATIONS
KW  - NOTCH1
UR  - http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true
L2  - http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true
N2  - 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.
ER  -

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 a F. DAMM. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. \textit{Leukemia}. London: Nature Publishing Group, 2017, roč.~31, č.~7, s.~1547-1554. ISSN~0887-6924. Dostupné z: https://doi.org/10.1038/leu.2016.359.

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