title: Quantitative analyses of DAPK1 methylation in AML and MDS.
abstract: Aberrant DNA methylation and concomitant transcriptional silencing of death-associated protein kinase 1 (DAPK1) have been demonstrated to be key pathogenic events in chronic lymphocytic leukemia (CLL). In acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), however, the presence of elevated DNA methylation levels has been a matter of continued controversy. Several studies demonstrated highly variable frequencies of DAPK1 promoter methylation by the use of methylation-specific PCR (MSP). By quantitative high-resolution assessment, we demonstrate that aberrant DNA methylation is an extremely rare event in this region. We observed elevated levels just in one out of 246 (0.4%) AML patients, all 42 MDS patients were unmethylated. In conclusion, we present a refined DAPK1 methylation analysis in a large representative patient cohort of AML and MDS patients proofing almost complete absence of elevated DNA methylation. Our results highlight the importance of quantitative measurements for translational research questions on primary patient specimens, particularly.
authors.affiliation: Department of Epigenomics and Cancer Risk Factors, German Cancer Research Center, DKFZ, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Claus
authors.forename: Björn
authors.initials: B
authors.lastname: Hackanson
authors.forename: Anna R
authors.initials: AR
authors.lastname: Poetsch
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.forename: Miriam
authors.initials: M
authors.lastname: Sonnet
authors.forename: Nadja
authors.initials: N
authors.lastname: Blagitko-Dorfs
authors.forename: Jan
authors.initials: J
authors.lastname: Hiller
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Oliver
authors.initials: O
authors.lastname: Galm
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D051017:Apoptosis Regulatory Proteins; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases