title: Characterization of CEBPA mutations in acute myeloid leukemia: most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells.
abstract: OBJECTIVE
  The transcription factor CCAAT/enhancer binding protein alpha, encoded by the CEBPA, is crucial for the differentiation of immature granulocytes. Mutation of the CEBPA may play an important role in leukemogenesis and prognosis. We sought to characterize the CEBPA mutation in acute myeloid leukemia (AML) and to clarify if there is a distinct immunophenotype for leukemic cells with the mutation.
  
  
  METHODS
  One hundred and four patients with de novo AML were evaluated for the CEBPA mutation and immunophenotype of the leukemic cells.
  
  
  RESULTS
  Twenty-two distinct mutations were identified in 16 (15%) of 104 AML patients. Fourteen patients had biallelic mutations, mostly involving both the NH(2)-terminal TAD1 region and the COOH-terminal basic leucine zipper domain (bZIP). The mutations in the bZIP region were always tandem duplications and were located at hot-spot regions for topoisomerase II sites. Sequential study of the CEBPA mutations showed that the mutations disappeared at complete remission but the same mutations reappeared at relapse. None of the patients developed novel mutations during the follow-up period. Patients with CEBPA mutations had significantly higher incidences of CD7 (73%), CD15 (100%), CD34 (93%), and HLA-DR (93%) expression on the leukemic cells.
  
  
  CONCLUSIONS
  These data revealed that most AML with CEBPA mutations were associated with an immunophenotype of HLA-DR(+)CD7(+)CD13(+)CD14(-)CD15(+)CD33(+)CD34(+). The close relationship of CEBPA mutations with the leukemia status of the patients and the concordance of mutation in presenting and relapse samples implicate the CEBPA mutation as a potential marker for monitoring minimal residue disease.
authors.affiliation: Graduate Institute of Medical Technology, National Taiwan University, Taipei, Taiwan,
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: You-Chia
authors.initials: YC
authors.lastname: Yeh
authors.forename: Hwei-Ling
authors.initials: HL
authors.lastname: Shen
authors.forename: Fang-Hsien
authors.initials: FH
authors.lastname: Su
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Sheng-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020440:Gene Duplication; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D015703:Antigens, CD; D022763:CCAAT-Enhancer-Binding Protein-alpha; D006684:HLA-DR Antigens; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3