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

Official URL:https://doi.org/10.1038/leu.2016.359
PubMed:View item in PubMed
Creators Name:Young, E. and Noerenberg, D. and Mansouri, L. and Ljungstroem, V. and Frick, M. and Sutton, L.A. and Blakemore, S.J. and Galan-Sousa, J. and Plevova, K. and Baliakas, P. and Rossi, D. and Clifford, R. and Roos-Weil, D. and Navrkalova, V. 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 Nguyen-Khac, F. and Rassenti, L. and Li, J. and Kipps, T.J. and Stamatopoulos, K. and Pospisilova, S. and Zenz, T. and Oakes, C.C. and Strefford, J.C. and Rosenquist, R. and Damm, F.
Journal Title:Leukemia
Journal Abbreviation:Leukemia
Volume:31
Number:7
Page Range:1547-1554
Date:July 2017
Keywords:CLL, EGR2, Genetics, Mutations, Prognosis
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.
ISSN:0887-6924
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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