YOUNG, E., D. NOERENBERG, L. MANSOURI, V. LJUNGSTROM, M. FRICK, L. A. SUTTON, S. J. BLAKEMORE, J. GALAN-SOUSA, Karla PLEVOVÁ, P. BALIAKAS, D. ROSSI, R. CLIFFORD, D. ROOS-WEIL, Veronika NAVRKALOVÁ, B. DOERKEN, 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, Šárka POSPÍŠILOVÁ, T. ZENZ, C. C. OAKES, J. C. STREFFORD, R. ROSENQUIST and F. DAMM. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. Leukemia. London: Nature Publishing Group, 2017, vol. 31, No 7, p. 1547-1554. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/leu.2016.359. |
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@article{1386746, author = {Young, E. and Noerenberg, D. and Mansouri, L. and Ljungstrom, V. and Frick, M. and Sutton, L. A. and Blakemore, S. J. and GalanandSousa, J. and Plevová, Karla and Baliakas, P. and Rossi, D. and Clifford, R. and RoosandWeil, D. and Navrkalová, Veronika 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 NguyenandKhac, F. and Rassenti, L. and Li, J. and Kipps, T. J. and Stamatopoulos, K. and Pospíšilová, Šárka and Zenz, T. and Oakes, C. C. and Strefford, J. C. and Rosenquist, R. and Damm, F.}, article_location = {London}, article_number = {7}, doi = {http://dx.doi.org/10.1038/leu.2016.359}, keywords = {IDENTIFIES RECURRENT MUTATIONS; LRF CLL4 TRIAL; GENE-MUTATIONS; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTORS; CLONAL EVOLUTION; SF3B1 MUTATIONS; HIGH-THROUGHPUT; ATM MUTATIONS; NOTCH1}, language = {eng}, issn = {0887-6924}, journal = {Leukemia}, title = {EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia}, url = {http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true}, volume = {31}, year = {2017} }
TY - JOUR ID - 1386746 AU - Young, E. - Noerenberg, D. - Mansouri, L. - Ljungstrom, V. - Frick, M. - Sutton, L. A. - Blakemore, S. J. - Galan-Sousa, J. - Plevová, Karla - Baliakas, P. - Rossi, D. - Clifford, R. - Roos-Weil, D. - Navrkalová, Veronika - Doerken, 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. - Pospíšilová, Šárka - Zenz, T. - Oakes, C. C. - Strefford, J. C. - Rosenquist, R. - Damm, F. PY - 2017 TI - EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia JF - Leukemia VL - 31 IS - 7 SP - 1547-1554 EP - 1547-1554 PB - Nature Publishing Group SN - 08876924 KW - IDENTIFIES RECURRENT MUTATIONS KW - LRF CLL4 TRIAL KW - GENE-MUTATIONS KW - MYELODYSPLASTIC SYNDROMES KW - TRANSCRIPTION FACTORS KW - CLONAL EVOLUTION KW - SF3B1 MUTATIONS KW - HIGH-THROUGHPUT KW - ATM MUTATIONS KW - NOTCH1 UR - http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true L2 - http://www.nature.com/leu/journal/v31/n7/full/leu2016359a.html?foxtrotcallback=true N2 - 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. ER -
YOUNG, E., D. NOERENBERG, L. MANSOURI, V. LJUNGSTROM, M. FRICK, L. A. SUTTON, S. J. BLAKEMORE, J. GALAN-SOUSA, Karla PLEVOVÁ, P. BALIAKAS, D. ROSSI, R. CLIFFORD, D. ROOS-WEIL, Veronika NAVRKALOVÁ, B. DOERKEN, 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, Šárka POSPÍŠILOVÁ, T. ZENZ, C. C. OAKES, J. C. STREFFORD, R. ROSENQUIST and F. DAMM. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. \textit{Leukemia}. London: Nature Publishing Group, 2017, vol.~31, No~7, p.~1547-1554. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/leu.2016.359.
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