Suppressed CEBPA Function Is Associated with Favorable Prognosis in Normal Karyotype AML Patients

The myeloid transcription factor CEBPA is crucial for normal differentiation of granulocytes. In addition, genomic mutations and deregulated expression of CEBPA have been reported in specific subsets of patients with acute myeloid leukemia (AML). We here investigated the prognostic significance of CEBPA mRNA, CEBPA protein, and CEBPA function in 105 consecutive de novo AML patients with a particular focus on AML patients with a normal karyotype. We found that the DNA binding activity of CEBPA in normal karyotype AML patients as determined by an ELISA-based assay conferred significant prognostic information: normal karyotype AML patients with suppressed CEBPA function showed a better OS (p=0.0068) and DFS (p=0.0138) compared to patients with conserved CEBPA function. In addition, suppressed levels of the 42kDa CEBPA protein in these patients tended to predict favorable outcome, whereas differences in p30 CEBPA protein levels and in mRNA expression did not affect the outcome. Finally, AML patients with suppressed CEBPA function had more frequently FLT3-ITD and an unmutated nucleophosmin status identifying CEBPA function as an independent prognostic marker for normal karyotype AML. This is the first study comprehensively assessing CEBPA transcription factor function in leukemic cells from AML patients. Our data suggest that suppressed CEBPA function is associated with favorable prognosis in normal karyotype AML patients independently of other molecular markers, and we propose assessment of CEBPA binding activity to be integrated into clinical practice. Moreover, our results highlight the importance of posttranscriptional mechanisms of CEBPA modulation in AML.