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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 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 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 Asnafi, V. Articles by Macintyre, E. Search for Related Content PubMed PubMed Citation Articles by Asnafi, V. Articles by Macintyre, E. Related Collections Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study Vahid Asnafi1,2,*, Agnès Buzyn1,*, Sandrine Le Noir1,2,*, Frédéric Baleydier1,2, Arnauld Simon1, Kheira Beldjord1,2, Oumedaly Reman3, Francis Witz4, Thierry Fagot5, Emmanuelle Tavernier6, Pascal Turlure7, Thibaut Leguay8, Françoise Huguet9, Jean-Paul Vernant10, Francis Daniel9, Marie-Christine Béné4, Norbert Ifrah11, Xavier Thomas12, Hervé Dombret13, and Elizabeth Macintyre1,2 1 Université Paris 5 Descartes and Assistance Publique Hôpitaux de Paris (AP-HP) and Hematology Department, Hôpital Necker-Enfants-Malades, Paris; 2 Institut National de la Santé et de la Recherche Médicale (INSERM) EMI0210; 3 Department of Hematology, Centre Hospitalier, Caen; 4 Department of Hematology and laboratoire d'immunophénotypage, Hôpitaux de Brabois, Vandoeuvre les Nancy; 5 Department of Hematology, Hôpital d'Instruction des Armées Percy, Clamart; 6 Department of Hematology, Institut de Cancérologie de la Loire, St Priest en Jarez; 7 Department of Hematology, Centre Hospitalier Dupuytren, Limoges; 8 Department of Hematology, Centre Hospitalier du Haut Lévêque, Pessac; 9 Department of Hematology, Hôpital Purpan, Toulouse; 10 Department of Hematology, Hôpital Pitié Salpétrière, Paris; 11 Department of Hematology, Centre Hospitalier, Angers; 12 Department of Hematology Hôpital Edouard Herriot, Lyon; and 13 Department of Hematology Hôpital St-Louis, Paris, France Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (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 among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1 mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P = .01) and not reached versus 32 months (P = .004) 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 = .02 and P = .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL. 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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