EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
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...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
3 January 2017
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| In: |
Leukemia
Year: 2017, Jahrgang: 31, Heft: 7, Pages: 1547-1554 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2016.359 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1038/leu.2016.359 Verlag, Volltext: https://www.nature.com/articles/leu2016359 
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| Verfasserangaben: | E. Young, D. Noerenberg, L. Mansouri, V. Ljungström, M. Frick, L.-A. Sutton, S.J. Blakemore, J. Galan-Sousa, K. Plevova, P. Baliakas, D. Rossi, R. Clifford, D. Roos-Weil, V. Navrkalova, B. Dörken, 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, S. Pospisilova, T. Zenz, C.C. Oakes, J.C. Strefford, R. Rosenquist and F. Damm |
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| 520 | |a 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. | ||
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