{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:17:57Z","timestamp":1792592277078,"version":"4.5.0"},"reference-count":27,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5694","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,10,8]]},"abstract":"<jats:p>\n                    Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    , a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and\/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.\n                  <\/jats:p>","DOI":"10.1126\/science.1102160","type":"journal-article","created":{"date-parts":[[2004,10,7]],"date-time":"2004-10-07T16:38:12Z","timestamp":1097167092000},"page":"269-271","source":"Crossref","is-referenced-by-count":2439,"title":["Activating Mutations of\n                    <i>NOTCH1<\/i>\n                    in Human T Cell Acute Lymphoblastic Leukemia"],"prefix":"10.1126","volume":"306","author":[{"given":"Andrew P.","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo A.","family":"Ferrando","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojoong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"John P.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryll","family":"Sanchez-Irizarry","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Blacklow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Thomas","family":"Look","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Aster","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00018-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90111-B"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80054-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00330-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8108"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.5.1825-1835.2000"},{"key":"e_1_3_2_8_2","unstructured":"C. Sanchez-Irizarry et al. Mol. Cell. Biol. in press."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00189-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1037392100"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.22.7812-7819.2002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.991602"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301567200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.20.7505-7515.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.11.3831-3842.2000"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.5.1906.h8001906_1906_1913"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.2.655-664.2003"},{"key":"e_1_3_2_18_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2000.52.pe1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101343200"},{"key":"e_1_3_2_21_2","unstructured":"J. C. Aster A. A. Ferrando A. P. Weng unpublished data."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02040"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.1.99"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.4.925"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023001"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd938"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311652200"},{"key":"e_1_3_2_28_2","unstructured":"We thank M. Wolfe for compound E and J.-P. Hezel for expert technical assistance. Supported by NIH grants CA82308 (J.C.A.) CA68484 and CA109901 (A.T.L.) CA94233 (S.C.B.) CA98093 (A.P.W.) and CA21765 (St. Jude Cancer Center). A.A.F. is a fellow of the Leukemia and Lymphoma Society."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1102160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:21:18Z","timestamp":1704842478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1102160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,8]]},"references-count":27,"journal-issue":{"issue":"5694","published-print":{"date-parts":[[2004,10,8]]}},"alternative-id":["10.1126\/science.1102160"],"URL":"https:\/\/doi.org\/10.1126\/science.1102160","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1021504.248633","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1021504.247615","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1021504.257615","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,8]]}}}