Publication Date:
2007-11-16
Description:
CCAAT/enhancer binding protein α (C/EBPα) is a master regulator for myeloid differentiation. As a potential tumor suppressor, its loss of function through mutations and posttranslational mechanisms has been thoroughly investigated in acute myeloid leukemia (AML). Recently, we have demonstrated the importance of epigenetic alterations in deregulating C/EBPα expression patterns in lung cancer and head and neck squamous cell carcinoma (HNSCC). In this study we investigated the role of DNA methylation and other epigenetic factors in the regulation of C/EBPα in AML using 94 patient samples and 7 leukemia cell lines. A comprehensive and quantitative DNA methylation analysis of C/EBPα’s large CpG island using MassARRAY (Sequenom©) technology and BioCOBRA identified a distinct and densely methylated upstream promoter region (−1423 bp to −1121 bp in relation to the transcription start site) in 20% (19 of 94) of AML patient samples and in five of seven leukemia cell lines, while the core promoter remained unmethylated. This aberrant DNA methylation pattern was associated with two generally prognostically favorable cytogenetic subgroups: inv(16)(p13q22) and t(15;17)(q22;q21). While DNA methylation levels in normal bone marrow samples (NBM) were very low (median: 0%, range: 0%–5%) when compared to NBM, we observed significantly higher DNA methylation levels in the inv(16) and t(15;17) cytogenetic subgroups, with median DNA methylation levels of 29% (range: 1% to 81%) and 5% (range: 1% to 94%), respectively (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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