Annals of Hematology

, Volume 91, Issue 1, pp 1–7

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

  • Oscar Fuster
  • Eva Barragán
  • Pascual Bolufer
  • Esperanza Such
  • Ana Valencia
  • Mariam Ibáñez
  • Sandra Dolz
  • Inmaculada de Juan
  • Antonio Jiménez
  • Maria Teresa Gómez
  • Ismael Buño
  • Joaquín Martínez
  • José Cervera
  • Pau Montesinos
  • Federico Moscardó
  • Miguel Ángel Sanz
Original Article

DOI: 10.1007/s00277-011-1234-z

Cite this article as:
Fuster, O., Barragán, E., Bolufer, P. et al. Ann Hematol (2012) 91: 1. doi:10.1007/s00277-011-1234-z

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.

Keywords

CEBPA Mutations Screening Intermediate risk Acute myeloid leukemia 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Oscar Fuster
    • 1
  • Eva Barragán
    • 1
  • Pascual Bolufer
    • 1
  • Esperanza Such
    • 2
  • Ana Valencia
    • 2
  • Mariam Ibáñez
    • 2
  • Sandra Dolz
    • 1
  • Inmaculada de Juan
    • 1
  • Antonio Jiménez
    • 3
  • Maria Teresa Gómez
    • 4
  • Ismael Buño
    • 5
  • Joaquín Martínez
    • 6
  • José Cervera
    • 2
  • Pau Montesinos
    • 2
  • Federico Moscardó
    • 2
  • Miguel Ángel Sanz
    • 2
  1. 1.Laboratory of Molecular Biology, Department of Medical PathologyHospital Universitario La FeValenciaSpain
  2. 2.Hematology DepartmentHospital Universitario La FeValenciaSpain
  3. 3.Hematology DepartmentHospital Universitario Carlos HayaMálagaSpain
  4. 4.Hematology DepartmentHospital Universitario Dr NegrínLas PalmasSpain
  5. 5.Hematology DepartmentHospital Gregorio MarañonMadridSpain
  6. 6.Hematology DepartmentHospital Universitario 12 de OctubreMadridSpain

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