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Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes *
Author(s) -
Potapova Anna,
Hasemeier Britta,
Römermann Daniel,
Metzig Kathleen,
Göhring Gudrun,
Schlegelberger Brigitte,
Länger Florian,
Kreipe Hans,
Lehmann Ulrich
Publication year - 2010
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2009.01389.x
Subject(s) - epigenetics , methylation , dna methylation , myelodysplastic syndromes , gene , biology , cancer research , genetics , bioinformatics , gene expression , medicine , immunology , bone marrow
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 < 0.05). In conclusion, epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in MDS. Patients with an isolated 5q‐deletion seem to harbour a distinct epigenetic profile.