Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes

The identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplastic syndromes (MDS). We therefore investigated the methylation status of transcription factor genes KLF5, KLF11, a...

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Bibliographic Details
Published in:European journal of haematology 2010-04, Vol.84 (4), p.298-303
Main Authors: Potapova, Anna, Hasemeier, Britta, Römermann, Daniel, Metzig, Kathleen, Göhring, Gudrun, Schlegelberger, Brigitte, Länger, Florian, Kreipe, Hans, Lehmann, Ulrich
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Cell Cycle Proteins - biosynthesis
Cell Cycle Proteins - genetics
DNA Methylation
Epigenesis, Genetic
epigenetics
Female
Gene Silencing
Genes, Tumor Suppressor
Humans
KLF11
Kruppel-Like Transcription Factors - biosynthesis
Kruppel-Like Transcription Factors - genetics
MafB Transcription Factor - biosynthesis
MafB Transcription Factor - genetics
Male
Middle Aged
myelodysplastic syndromes
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - metabolism
Repressor Proteins - biosynthesis
Repressor Proteins - genetics
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Summary:The identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplastic syndromes (MDS). We therefore investigated the methylation status of transcription factor genes KLF5, KLF11, and MAFB, shown to be aberrantly methylated in myelogeneous leukaemia cells, in a series of 115 MDS patient as well as in 25 control subjects. Using quantitative high‐resolution pyrosequencing methodology, KLF11, MAFB, and KLF5 were shown for the first time to be hypermethylated in 17 (15%), 8 (7%), and 2 (1.7%) cases, respectively, but not in any of the patients with an isolated 5q‐deletion. Patient samples harbouring KLF11 methylation displayed reduced KLF11 mRNA expression and KLF11 hypermethylation correlated with a high International Prognostic Scoring System score (P 
ISSN:0902-4441
1600-0609
DOI:10.1111/j.1600-0609.2009.01389.x