| Autor: |
Young, E. Noerenberg, D. Mansouri, L. Ljungström, V. Frick, M. Sutton, L.-A. Blakemore, S.J. Galan-Sousa, J. Plevova, K. Baliakas, P. Rossi, D. Clifford, R. Roos-Weil, D. Navrkalova, V. Dörken, 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. Pospisilova, S. Zenz, T. Oakes, C.C. Strefford, J.C. Rosenquist, R. Damm, F. |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Popis: |
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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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