1. ¹Division of Hematology-Oncology, Medizinische Hochschule Hannover, Germany
2. ²Division of Hematology-Oncology, Heinrich-Heine University Düsseldorf, Germany
3. ³Division of Hematology Cedars-Sinai Medical Center, Los Angeles, CA, USA

Correspondence: W Verbeek, Division of Hematology-Oncology, Klinikum Braunschweig, Celler Str 38, 38114 Braunschweig, Germany; Fax: 049 (0)531-5953757

Received 27 July 2001; Accepted 25 September 2002.

Abstract

Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBP) have been described in acute myeloid leukemia (AML). We performed a mutational analysis of the C/EBP 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/EBP 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/EBP isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBP 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/EBP mutation was not essential for the initial blast accumulation. The emergence of a bast clone carrying a C/EBP mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.