{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:29:48Z","timestamp":1791174588391,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"26","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2009,9,10]]},"abstract":"Purpose<\/jats:title> Notch pathway activation by mutations in either NOTCH1 and\/or FBXW7 is one of the most common molecular events in T-cell acute lymphoblastic leukemia (T-ALL) and, in pediatric disease, predicts for favorable outcome. Their prognostic significance in adult T-ALL is unclear. We sought to evaluate the outcome according to mutation status of patients with adult T-ALL treated on the United Kingdom Acute Lymphoblastic Leukaemia XII (UKALLXII)\/Eastern Cooperative Oncology Group (ECOG) E2993 protocol. <\/jats:p><\/jats:sec>Methods<\/jats:title> NOTCH1 and FBXW7 were screened by a combination of denaturing high-performance liquid chromatography and sequencing in 88 adult patients with T-ALL treated on the UKALLXII\/ECOG E2993 protocol and compared with clinical characteristics and outcome. <\/jats:p><\/jats:sec>Results<\/jats:title> NOTCH1 and FBXW7 mutations were common (60% and 18%, respectively) and were not associated with age or WBC count. NOTCH1 heterodimerization domain mutations were associated with FBXW7 mutations (P = .02), and NOTCH1 proline, glutamic acid, serine, threonine (PEST) rich domain and FBXW7 mutations were mutually exclusive. There were an equal number of high- and standard-risk patients in the NOTCH1 and FBXW7 mutated (MUT) groups. Patients wild type (WT) for both markers trended toward poorer event-free survival (EFS; MUT v WT, 51% v 27%, P = .10; hazard ratio, 0.6). Analysis by each marker individually was not significantly predictive of outcome (NOTCH1 MUT v WT, EFS 49% v 34%, P = .20; FBXW7 MUT v WT, EFS 53% v 41%, P.72). <\/jats:p><\/jats:sec>Conclusion<\/jats:title> NOTCH1 and FBXW7 mutant-positive patients do not fare sufficiently well to warrant an individualized treatment approach in future studies. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.22.0996","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T01:47:06Z","timestamp":1248745626000},"page":"4352-4356","source":"Crossref","is-referenced-by-count":105,"title":["Prognostic Implications of NOTCH1<\/i> and FBXW7<\/i> Mutations in Adults With T-Cell Acute Lymphoblastic Leukemia Treated on the MRC UKALLXII\/ECOG E2993 Protocol"],"prefix":"10.1200","volume":"27","author":[{"given":"Marc R.","family":"Mansour","sequence":"first","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Sulis","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Duke","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Foroni","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Koo","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Allen","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary E.","family":"Gale","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; 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Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Paietta","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Tallman","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; 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Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Linch","sequence":"additional","affiliation":[{"name":"From the Department of Haematology, Cancer Institute, and University College London Hospital; Imperial College, Hammersmith Hospital Campus, London; Clinical Trial Service Unit, Oxford, United Kingdom; Department of Pediatric Oncology, Columbia University Medical Center; Institute for Cancer Genetics and Department of Pathology, Columbia University Medical Center, New York; Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY; Rambam Medical Center and Technion, Israel Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V71.1.123.123"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400959"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-051912"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1102160"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404101"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606108103"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1450406"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-039883"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1636"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nm1524"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070872"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-130096"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature05886"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4381"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2008.03.040"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-4956"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2832"},{"key":"B18","author":"Asnafi V","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1623"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1474"},{"key":"B21","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1182\/blood-2007-10-116582","volume":"111","author":"Goldstone AH","year":"2008","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-037093"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2708"},{"key":"B24","first-page":"1126","volume":"87","author":"Gameiro P","year":"2002","journal-title":"Haematologica"},{"key":"B25","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1038\/sj.leu.2403081","volume":"17","author":"Szczepa\u0144ski T","year":"2003","journal-title":"Leukemia"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4386"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070876"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15542-6"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-015826"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2009.22.0996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T23:29:55Z","timestamp":1653521395000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2009.22.0996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,10]]},"references-count":29,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2009,9,10]]}},"alternative-id":["10.1200\/JCO.2009.22.0996"],"URL":"https:\/\/doi.org\/10.1200\/jco.2009.22.0996","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,10]]}}}