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| Item Type: | Article |
|---|---|
| Title: | EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia |
| Creators Name: | 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. and Damm, F. |
| 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. |
| Keywords: | CLL, EGR2, Genetics, Mutations, Prognosis |
| Source: | Leukemia |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Volume: | 31 |
| Number: | 7 |
| Page Range: | 1547-1554 |
| Date: | July 2017 |
| Official Publication: | https://doi.org/10.1038/leu.2016.359 |
| PubMed: | View item in PubMed |
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