EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
| Autor: | Young, E, Noerenberg, D, Mansouri, L, Ljungström, V, Frick, M, Sutton, L-A, Blakemore, SJ, Galan-Sousa, J, Plevova, K, Baliakas, P, Rossi, D, Clifford, R, Roos-Weil, D, Navrkalova, V, Dörken, B, Schmitt, CA, Smedby, KE, Juliusson, G, Giacopelli, B, Blachly, JS, Belessi, C, Panagiotidis, P, Chiorazzi, N, Davi, F, Langerak, AW, Oscier, D, Schuh, A, Gaidano, G, Ghia, P, Xu, W, Fan, L, Bernard, OA, Nguyen-Khac, F, Rassenti, L, Li, J, Kipps, TJ, Stamatopoulos, K, Pospisilova, S, Zenz, T, Oakes, CC, Strefford, JC, Rosenquist, R, Damm, F |
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| Přispěvatelé: | Immunology, 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, PAOLO PROSPERO, 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 |
| Předmět: |
p53
Adult Male Cancer Research Lymphoma Clinical Sciences Oncology and Carcinogenesis Immunology Article Rare Diseases Clinical Research Genetics Humans Chronic neoplasms Early Growth Response Protein 2 Cancer Aged Proportional Hazards Models screening and diagnosis Leukemia B-Cell Hematology Middle Aged Genes p53 Leukemia Lymphocytic Chronic B-Cell Lymphocytic 4.1 Discovery and preclinical testing of markers and technologies Detection Anesthesiology and Pain Medicine Genes Mutation Female |
| Zdroj: | Sygma Institutional Repository for Molecular Medicine (MDC) Leukemia, 31(7), 1547-1554. Nature Publishing Group Leukemia, vol 31, iss 7 |
| ISSN: | 0887-6924 |
| DOI: | 10.1038/leu.2016.359 |
| 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.Leukemia advance online publication, 3 January 2017; doi:10.1038/leu.2016.359. |
| Databáze: | OpenAIRE |
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