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Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia

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Abstract

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein α (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16–80 years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1–5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n = 12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0–13.2, p = 0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0–17.4, p = 0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.

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Acknowledgments

This study was partially supported by the grants “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III” 06/0657, “Red Temática de Investigación Cooperativa en Cancer” RD06/0020/0031, “Ministerio de Ciencia e Innovación” BES2008-0080539, “Contrato de técnicos de apoyo a la investigación en el Sistema Nacional de Salud” CA08/00141, and “X Contratos de investigación para postresidentes-Instituto de Investigación Sanitaria, Fundación de Investigación Hospital La Fe-”. We also are grateful to Biobanco La Fe for supplying biological samples (RD09/0076/00021).

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Department of Medical Pathology, Hospital Universitario La Fe, Escuela de enfermería 7ª planta., Avd. Campanar 21, Valencia, 46009, Spain

    Oscar Fuster, Eva Barragán, Pascual Bolufer, Sandra Dolz & Inmaculada de Juan

  2. Hematology Department, Hospital Universitario La Fe, Valencia, Spain

    Esperanza Such, Ana Valencia, Mariam Ibáñez, José Cervera, Pau Montesinos, Federico Moscardó & Miguel Ángel Sanz

  3. Hematology Department, Hospital Universitario Carlos Haya, Málaga, Spain

    Antonio Jiménez

  4. Hematology Department, Hospital Universitario Dr Negrín, Las Palmas, Spain

    Maria Teresa Gómez

  5. Hematology Department, Hospital Gregorio Marañon, Madrid, Spain

    Ismael Buño

  6. Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Joaquín Martínez

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  1. Oscar Fuster
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  2. Eva Barragán
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Correspondence to Eva Barragán.

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Fuster, O., Barragán, E., Bolufer, P. et al. Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia. Ann Hematol 91, 1–7 (2012). https://doi.org/10.1007/s00277-011-1234-z

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  • DOI: https://doi.org/10.1007/s00277-011-1234-z

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