title: A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation.
abstract: C/EBPalpha plays an essential role as a transcription factor in myeloid cell differentiation. Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4-base pair insertion in the N-terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107). The father and a son at diagnosis of AML had different in-frame insertion mutations in the C-terminal region of C/EBPalpha. These C-terminal mutations disappeared upon remission in both patients. Interestingly, the father showed different in-frame insertion mutations in the C-terminal CEBPA at the time of diagnosis and relapse. These data strongly suggest that the N-terminal C/EBPalpha mutation predisposes to the occurrence of a C-terminal C/EBPalpha mutation as a secondary genetic hit, causing AML.
authors: Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan.
authors: Tomoko
authors: T
authors: Nanri
authors: Naokuni
authors: N
authors: Uike
authors: Toshiro
authors: T
authors: Kawakita
authors: Eisaku
authors: E
authors: Iwanaga
authors: Hiroaki
authors: H
authors: Mitsuya
authors: Norio
authors: N
authors: Asou
mesh_terms: D000293:Adolescent; D000328:Adult; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D017931:DNA Primers; D004273:DNA, Neoplasm