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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3918-3924. Prepublished online as a Blood First Edition Paper on December 23, 2008; DOI 10.1182/blood-2008-10-184069. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2008-10-184069v1 113/17/3918    most recent Alert me when this article is cited Alert me if a correction is posted 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 Asnafi, V. Articles by Macintyre, E. Search for Related Content PubMed PubMed Citation Articles by Asnafi, V. Articles by Macintyre, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 17, 2008 Accepted December 4, 2008 NOTCH1/FBXW7 mutation identifies a large subgroup with favourable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a GRAALL study Vahid Asnafi, Agnes Buzyn, Sandrine Le Noir, Frederic Baleydier, Arnauld Simon, Kheira Beldjord, Oumedaly Reman, Francis Witz, Thierry Fagot, Emmanuelle Tavernier, Pascal Turlure, Thibaut Leguay, Francoise Huguet, Jean-Paul Vernant, Francis Daniel, Marie-Christine Bene, Norbert Ifrah, Xavier Thomas, Herve Dombret, and Elizabeth Macintyre* Universite Paris 5 Descartes and Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker-Enfants-Malades, Paris, France Institut National de la Sante et de la Recherche Medicale (INSERM) EMI0210, Paris, France Department of Hematology, Centre Hospitalier, Caen, France Department of Hematology and laboratoire d'immunophenotypage, Hopitaux de Brabois, Vandoeuvre les Nancy, France Department of Hematology, Hopitaux d'Instuction des Armees Percy, Clamart, France Department of Hematology, Institut de Cancerologie de la Loire, St Priest en Jarez, France Department of Hematology, Centre Hospitalier Dupuytren, Limoges, France Department of Hematology, Centre Hospitalier du Haut Leveque, Pessac, France Department of Hematology, Hopital Purpan, Toulouse, France Department of Hematology, Hopital Pitie Salpetriere, Paris, France Department of Hematology, Centre Hospitalier, Angers, France Department of Hematology, Hopital Edouard Herriot, Lyon, France Department of Hematology, Hopital St-Louis, Paris, France * Corresponding author; email: elizabeth.macintyre{at}nck.aphp.fr. Many somatic genetic abnormalities have been identified in T-ALL but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are amongst the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the LALA-94 (n=87) or the GRAALL-2003 (n=54) trials. 88 cases (62%) demonstrated NOTCH1 mutations (42% HD, 10% HD+PEST, 6% PEST, 2% juxtamembrane mutations, 2% TAD) and 34 cases (24%) FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biological features. Median EFS and OS were 36 versus 17 months (P=0.01) and not reached versus 32 months (P=0.0035) in patients with NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent good prognostic factor for EFS and OS (P=0.02 and P=0.01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favourable outcome that could justify individual therapeutic stratification for T-ALL. This study is registered at http://clinicaltrials.gov as NCT00222027. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. G. Mullighan Mutations of NOTCH1, FBXW7, and prognosis in T-lineage acute lymphoblastic leukemia Haematologica, October 1, 2009; 94(10): 1338 - 1340. [Full Text] [PDF] C. D. Baldus, J. Thibaut, N. Goekbuget, A. Stroux, C. Schlee, M. Mossner, T. Burmeister, S. Schwartz, C. D. Bloomfield, D. Hoelzer, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia Haematologica, October 1, 2009; 94(10): 1383 - 1390. [Abstract] [Full Text] [PDF]

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