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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1151-1157. Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2005-12-4956. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-12-4956v1 108/4/1151    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Breit, S. Articles by Kulozik, A. E. Search for Related Content PubMed PubMed Citation Articles by Breit, S. Articles by Kulozik, A. E. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia Stephen Breit, Martin Stanulla, Thomas Flohr, Martin Schrappe, Wolf-Dieter Ludwig, Gabriele Tolle, Margit Happich, Martina U. Muckenthaler, and Andreas E. Kulozik From the Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg; the Department of Pediatric Hematology and Oncology, Hannover Medical School; the Institute of Human Genetics, University of Heidelberg; the Department of General Pediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel; and the Department of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Clinic at the HELIOS Clinic Berlin-Buch, Charité Medical School, Berlin, Germany. Activating mutations of the transmembrane receptor NOTCH1 are common in precursor T-cell lymphoblastic leukemia (T-ALL). We systematically analyzed the impact of activating NOTCH1 mutations on early treatment response and long-term outcome in 157 patients with T-ALL of the pediatric ALL–Berlin-Frankfurt-Munster (BFM) 2000 study. We confirm previous results that NOTCH1 mutations occur in more than 50% of T-ALL in children. In 82 patients (82/157; 52.2%), activating NOTCH1 mutations were identified either in the heterodimerization (55/82; 67.1%), in the PEST (13/82; 15.9%), or in both domains (14/82; 17.0%). The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease (MRD) kinetics, which was independent from sex, age, white blood cell count, and T-cell immunophenotype at the time of diagnosis. Furthermore, activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis. These findings indicate that in the context of the ALL-BFM 2000 treatment strategy, NOTCH1 mutations predict a more rapid early treatment response and a favorable long-term outcome in children with T-ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: NOTCH1: prognostic factor or molecular target? Stephen P. Hunger Blood 2006 108: 1117-1118. 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