Purpose: The transcription factor CCAAT/enhancer binding protein α, 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.

Experiment Design: 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 NH₂-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.

Conclusion: 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.