The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication.

Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA(+) de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapse-free, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P = .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA(+) AML (multivariate hazard ratio = 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively).

[1]  Christian Langer,et al.  Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Axel Benner,et al.  Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. , 2008, The New England journal of medicine.

[3]  C. Preudhomme,et al.  Cooperating gene mutations in acute myeloid leukemia: a review of the literature , 2008, Leukemia.

[4]  J. Bourhis,et al.  Randomized Comparison of Standard Induction with Daunorubicin (DNR) for 3 Days vs Idarubicin (IDA) for 3 or 4 Days in AML pts Aged 50 to 70 and of Maintenance with Interleukin 2. Final Analysis of the ALFA 9801 Study. , 2007 .

[5]  T. Pabst,et al.  Transcriptional dysregulation during myeloid transformation in AML , 2007, Oncogene.

[6]  J. Bourhis,et al.  Effect of priming with granulocyte–macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group , 2007, Leukemia.

[7]  J. Cayuela,et al.  Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. , 2005, Blood.

[8]  M. Fey,et al.  Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype , 2005, Clinical Cancer Research.

[9]  H. Dombret,et al.  Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. , 2004, Blood.

[10]  S. Fröhling,et al.  CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  J. Cayuela,et al.  Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). , 2002, Blood.

[12]  X Thomas,et al.  Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy , 2002, Leukemia.

[13]  K Wheatley,et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. , 1998, Blood.

[14]  Bob Löwenberg,et al.  Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML. , 2003, The hematology journal : the official journal of the European Haematology Association.