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, 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.
Potapova
Anna
A
Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.
Hasemeier
Britta
B
Römermann
Daniel
D
Metzig
Kathleen
K
Göhring
Gudrun
G
Schlegelberger
Brigitte
B
Länger
Florian
F
Kreipe
Hans
H
Lehmann
Ulrich
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D051258:MafB Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C115117:KLF11 protein, human; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D012097:Repressor Proteins