Aberrant DNA methylation of the transcription factor C/EBPα in acute myelogenous leukemia

We investigated the methylation status of the CCAAT/enhancer binding protein alpha (C/EBPα) promoter region near the transcription start site in acute myelogenous leukemia (AML). In hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBPα promoter region was associated with transcriptional silencing, and treatment with the demethylating agent 5-aza-2′-deoxycytidine resulted in C/EBPα reexpression and promoter demethylation. Aberrant methylation of the C/EBPα promoter region occurred in 10/80 diagnostic AML samples, and there was an inverse correlation between aberrant methylation of C/EBPα and the negative cell cycle regulator p15. Our results provide further evidence for epigenetic dysregulation of C/EBPα in AML.