Abstract
Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBPα) have been described in acute myeloid leukemia (AML). We performed a mutational analysis of the C/EBPα gene in the myelodysplastic syndromes and AML with antecedent MDS. No mutations were found in patients with refractory anemia (0/27), refractory anemia with ringed sideroblasts (0/7), refractory anemia with excess of blasts (RAEB 0/16) or chronic myelomonocytic leukemia (CMML 0/5). One out of 13 patients with RAEB-T/AML secondary to MDS showed a mutation in the C/EBPα gene. In this patient a 4 bp insertion disrupted codon 69 in one allele. This novel +1 frame shift is predicted to result in a truncated protein of 107 amino acids. However, the dominant protein translated was the C/EBPα isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBPα p42. Interestingly this mutation could not be detected at diagnosis in the initial RAEB and RAEB-T stage. The mutation appeared at relapse after chemotherapy for RAEB-T. We conclude that the C/EBPα mutation was not essential for the initial blast accumulation. The emergence of a bast clone carrying a C/EBPα mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.
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Acknowledgements
This work was in part supported by the Kompetenznetzwerk Acute and Chronic Leukemias, Germany and the Dieter-Schlag-Stiftung for Leukemia Research.
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Kaeferstein, A., Krug, U., Tiesmeier, J. et al. The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML. Leukemia 17, 343–349 (2003). https://doi.org/10.1038/sj.leu.2402805
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DOI: https://doi.org/10.1038/sj.leu.2402805