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

Autores de IIS La Fe

• Oscar Fuster Lluch

  Autor

• Eva Barragán González

  Autor

• Pascual Bolufer Gilabert

  Autor

• Esperanza Such Taboada

  Autor

• Ana Belen Valencia Martinez

  Autor

• Maria Amparo Ibañez Company

  Autor

• Sandra Dolz Giménez

  Autor

• Inmaculada De Juan Jiménez

  Autor

• Jesus Antonio Martinez Dominguez

  Autor

• José Vicente Cervera Zamora

  Autor

• Pau Montesinos Fernández

  Autor

• Federico Moscardo Garcia

  Autor

• 

  Miguel Ángel Sanz Alonso

  Autor

Participantes ajenos a IIS La Fe

• Jiménez A
• Gómez MT
• Buño I

Grupos

• Hematología y Hemoterapia

  

  Investigador Principal

  Javier De La Rubia Comos

• Investigación Clínica y Traslacional en Cáncer

  

  Leader

  José Gómez Codina

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 a (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.