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 Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-03-0990.

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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2717-2723

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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, Stéphane de Botton, Xavier Thomas, Emmanuel Raffoux, Charlotte Lamandin, Sylvie Castaigne, Pierre Fenaux, and Hervé Dombret for the ALFA Group

From the Département d'Hématologie and INSERM U524, Hôpital Claude Huriez, Lille, France; Département d'Hématologie and INSERM U462, Hôpital Saint-Louis, Paris, France; and Département d'Hématologie, Hôpital Edouard Herriot, Lyon, France.

The transcription factor C/EBPalpha 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 (French-American-British [FAB]-M3 excluded). All patients were prospectively enrolled between 1990 and 1996 in a multicenter trial of the ALFA (Acute Leukemia French Association) 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 (11%) of 135 patients tested. 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/EBPalpha 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 of 15 CEBPA-mutated as compared with 30 of 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% vs 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.

© 2002 by The American Society of Hematology.
 

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