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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-03-0990. This Article Full Text (PDF) All Versions of this Article: 2002-03-0990v1 100/8/2717    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 Preudhomme, C. Articles by Dombret, H. Search for Related Content PubMed PubMed Citation Articles by Preudhomme, C. Articles by Dombret, H. Social Bookmarking                   What's this? Submitted March 29, 2002 Accepted June 6, 2002 Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA) Claude Preudhomme*, Christophe Sagot, Nicolas Boissel, Jean-Michel Cayuela, Isabelle Tigaud, Stephane de Botton, Xavier Thomas, Emmanuel Raffoux, Charlotte Lamandin, Sylvie Castaigne, Pierre Fenaux, and Herve Dombret Unite 524, INSERM, Lille, France; Departement d'Hematologie, Hopital Claude Huriez, Lille, France Unite 462, INSERM, Paris, France Unite 462, INSERM, Paris, France; Departement d'Hematologie, Hopital Saint Louis, Paris, France Departement d'Hematologie, Hopital Edouard Herriot, Lyon, France Departement d'Hematologie, Hopital Claude Huriez, Lille, France Departement d'Hematologie, Hopital Saint Louis, Paris, France * Corresponding author; email: cpreudhomme{at}chru-lille.fr. The transcription factor C/EBP is crucial for differentiation of mature granulocytes. Recently, different CEBPA gene mutations likely to induce differentiation arrest have been described in nearly 10% of patients with acute myeloid leukemia (AML). In the present study, we retrospectively analyzed the prognostic significance of CEBPA mutations in 135 AML patients (FAB-M3 excluded). All patients were prospectively enrolled between 1990 and 1996 in a multicenter trial of the ALFA group (median age, 45 years; median follow-up, 5.7 years). Mutations were assessed using direct sequencing of the CEBPA gene. Twenty-two mutations were found in 15/135 patients tested (11%). Twelve patients had at least one mutation located in the N-terminal part of the protein leading to the lack of expression of the full-length C/EBP protein. CEBPA mutations were present only in patients belonging to the intermediate cytogenetic risk subgroup and associated with the FAB-M1 subtype (P=.02). FLT3 internal tandem duplication (ITD) was found in 5/15 CEBPA mutated as compared to 30/119 CEBPA nonmutated cases tested (P=.54). Presence of CEBPA mutations was identified as an independent good-prognosis factor for outcome even after adjustment on cytogenetics and FLT3 status (estimated 5-year overall survival, 53% versus 25%; P=.04). FLT3-ITD appeared to act as a major bad prognosis factor in patients with CEBPA mutated AML. We thus propose a risk classification that includes in the favorable subgroup all patients from the intermediate subgroup displaying CEBPA mutations when not associated with FLT3-ITD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Heuser, L. M. Sly, B. Argiropoulos, F. Kuchenbauer, C. Lai, A. Weng, M. Leung, G. Lin, C. Brookes, S. Fung, et al. 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