Evidence for allelic evolution of C/EBPalpha mutations in acute myeloid leukaemia

Br J Haematol. 2003 Nov;123(3):413-9. doi: 10.1046/j.1365-2141.2003.04618.x.


Transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is mutated in 6-10% of patients with acute myeloid leukaemia (AML). Recently, we reported the emergence of an N-terminal C/EBPalpha mutation after chemotherapy in a patient with secondary AML. The clone carrying the mutation became the dominant clone at relapse. This observation prompted us to compare the C/EBPalpha mutational status of 26 de novo non-core binding factor AML patients at diagnosis and at relapse after induction and consolidation chemotherapy. Four mutations in the C/EBPalpha gene were identified in two out of 26 patients. In both these cases, a biallelic mutation was present at diagnosis and at relapse: an amino-terminal frameshift mutation and a mutation of the fork/leucine finger 1 region. In patient 1, the amino-terminal frameshift mutation was duplicated and found on both alleles at relapse. In patient 2, the amino-terminal frameshift mutation and a mutation in the fork region were found either alone or combined on the same allele, suggesting a subclone formation. None of the patients without a C/EBPalpha mutation at diagnosis showed a mutation at relapse. This is the first report of an evolution of the C/EBPalpha gene between diagnosis and relapse in AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Alleles
  • CCAAT-Enhancer-Binding Protein-alpha / genetics*
  • Clone Cells
  • Female
  • Frameshift Mutation
  • Humans
  • Leukemia, Myeloid / genetics*
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Recurrence
  • T-Lymphocytes


  • CCAAT-Enhancer-Binding Protein-alpha