title: Evidence for allelic evolution of C/EBPalpha mutations in acute myeloid leukaemia.
abstract: 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.
authors: Division of Hematology-Oncology, Medizinische Hochschule Hannover, Germany.
authors: Jens
authors: J
authors: Tiesmeier
authors: Andreas
authors: A
authors: Czwalinna
authors: Carsten
authors: C
authors: Müller-Tidow
authors: Jürgen
authors: J
authors: Krauter
authors: Hubert
authors: H
authors: Serve
authors: Gerhard
authors: G
authors: Heil
authors: Arnold
authors: A
authors: Ganser
authors: Walter
authors: W
authors: Verbeek
mesh_terms: D000208:Acute Disease; D000328:Adult; D000483:Alleles; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012008:Recurrence; D013601:T-Lymphocytes
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha