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1000 Titel
  • Genome-wide DNA methylation profiling is able to identify prefibrotic PMF cases at risk for progression to myelofibrosis
1000 Autor/in
  1. Lehmann, Ulrich |
  2. Stark, Helge |
  3. Bartels, Stephan |
  4. Schlue, Jerome |
  5. Büsche, Guntram |
  6. Kreipe, Hans |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-02-04
1000 Erschienen in
1000 Quellenangabe
  • 13(1):28
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13148-021-01010-y |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860011/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!Patients suffering from the BCR-ABL1-negative myeloproliferative disease prefibrotic primary myelofibrosis (pre-PMF) have a certain risk for progression to myelofibrosis. Accurate risk estimation for this fibrotic progression is of prognostic importance and clinically relevant. Commonly applied risk scores are based on clinical, cytogenetic, and genetic data but do not include epigenetic modifications. Therefore, we evaluated the assessment of genome-wide DNA methylation patterns for their ability to predict fibrotic progression in PMF patients.!##!Results!#!For this purpose, the DNA methylation profile was analyzed genome-wide in a training set of 22 bone marrow trephines from patients with either fibrotic progression (n = 12) or stable disease over several years (n = 10) using the 850 k EPIC array from Illumina. The DNA methylation classifier constructed from this data set was validated in an independently measured test set of additional 11 bone marrow trephines (7 with stable disease, 4 with fibrotic progress). Hierarchical clustering of methylation β-values and linear discriminant classification yielded very good discrimination between both patient groups. By gene ontology analysis, the most differentially methylated CpG sites are primarily associated with genes involved in cell-cell and cell-matrix interactions.!##!Conclusions!#!In conclusion, we could show that genome-wide DNA methylation profiling of bone marrow trephines is feasible under routine diagnostic conditions and, more importantly, is able to predict fibrotic progression in pre-fibrotic primary myelofibrosis with high accuracy.
1000 Sacherschließung
lokal Embryonic Germ Cells/metabolism [MeSH]
lokal Animal Experimentation [MeSH]
lokal Disease Progression [MeSH]
lokal Fibrosis/pathology [MeSH]
lokal Risk Factors [MeSH]
lokal Gene Ontology [MeSH]
lokal 850 k EPIC array
lokal Genome-Wide Association Study/methods [MeSH]
lokal Male [MeSH]
lokal DNA methylation
lokal Primary Myelofibrosis/genetics [MeSH]
lokal DNA Fingerprinting/methods [MeSH]
lokal Fusion Proteins, bcr-abl/genetics [MeSH]
lokal Female [MeSH]
lokal Humans [MeSH]
lokal Bone Marrow/metabolism [MeSH]
lokal Predictive Value of Tests [MeSH]
lokal Prefibrotic PMF
lokal Cellular Reprogramming Techniques/methods [MeSH]
lokal Epigenomics/methods [MeSH]
lokal Fibrosis/genetics [MeSH]
lokal Cell Competition/genetics [MeSH]
lokal CpG Islands/genetics [MeSH]
lokal Cancer epigenetics and diagnostics
lokal DNA Methylation [MeSH]
lokal Research
lokal Prognosis [MeSH]
lokal Primary Myelofibrosis/pathology [MeSH]
lokal Myelofibrosis
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-2350-6584|https://frl.publisso.de/adhoc/uri/U3RhcmssIEhlbGdl|https://frl.publisso.de/adhoc/uri/QmFydGVscywgU3RlcGhhbg==|https://frl.publisso.de/adhoc/uri/U2NobHVlLCBKZXJvbWU=|https://frl.publisso.de/adhoc/uri/QsO8c2NoZSwgR3VudHJhbQ==|https://frl.publisso.de/adhoc/uri/S3JlaXBlLCBIYW5z
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1000 Erstellt am 2023-11-15T23:21:16.952+0100
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