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.
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.
Lin
Liang-In
LI
Graduate Institute of Medical Technology, National Taiwan University, Taipei, Taiwan,
Chen
Chien-Yuan
CY
Lin
Dong-Tsamn
DT
Tsay
Woei
W
Tang
Jih-Luh
JL
Yeh
You-Chia
YC
Shen
Hwei-Ling
HL
Su
Fang-Hsien
FH
Yao
Ming
M
Huang
Sheng-Yi
SY
Tien
Hwei-Fang
HF
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
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