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- Title
The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML.
- Authors
Kaeferstein, A; Krug, U; Tiesmeier, J; Aivado, M; Faulhaber, M; Stadler, M; Krauter, J; Germing, U; Hofmann, W K; Koeffler, H P; Ganser, A; Verbeek, W
- 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.
- Subjects
TRANSCRIPTION factors; MYELOID leukemia
- Publication
Leukemia (08876924), 2003, Vol 17, Issue 2, p343
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2402805