Lise Lotte Hansen

Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Helene Myrtue Nielsen
  • Christen Lykkegaard Andersen, Roskilde Hosp, Dept Hematol
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  • Maj Westman, Rigshosp, University of Copenhagen, Dept Clin Genet
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  • Lasse Sommer Kristensen, Copenhagen Univ Hosp, University of Copenhagen, Dept Hematol, Rigshosp
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  • Fazila Asmar, Copenhagen Univ Hosp, University of Copenhagen, Dept Hematol, Rigshosp
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  • Torben Arvid Kruse, Odense Univ Hosp, Odense University Hospital, Dept Clin Genet
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  • Mads Thomassen, Odense Univ Hosp, Odense University Hospital, Dept Clin Genet
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  • Thomas Stauffer Larsen, Odense Univ Hosp, Odense University Hospital, Dept Hematol
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  • Vibe Skov, Roskilde Hosp, Dept Hematol
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  • Lise Lotte Hansen
  • Ole Weis Bjerrum, Copenhagen Univ Hosp, University of Copenhagen, Dept Hematol, Rigshosp
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  • Hans Carl Hasselbalch, Roskilde Hosp, Dept Hematol
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  • Vasu Punj, Univ Southern Calif, Keck Sch Med, Div Hematol
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  • Kirsten Gronbaek, Copenhagen Univ Hosp, University of Copenhagen, Dept Hematol, Rigshosp, Univ Copenhagen, University of Copenhagen, Danish Stem Cell Ctr DanStem, Fac Hlth Sci

This is the first study to compare genome-wide DNA methylation profiles of sorted blood cells from myelofibrosis (MF) patients and healthy controls. We found that differentially methylated CpG sites located to genes involved in 'cancer' and 'embryonic development' in MF CD34+ cells, in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation pattern using an unsupervised approach. However, in a supervised analysis of ASXL1 mutated versus wild-type cases, differentially methylated CpG sites were enriched in regions marked by histone H3K4me1, histone H3K27me3, and the bivalent histone mark H3K27me3 + H3K4me3 in human CD34+ cells. Hypermethylation of selected CpG sites was confirmed in a separate validation cohort of 30 MF patients by pyrosequencing. Altogether, we show that individual MF cell populations have distinct differentially methylated genes relative to their normal counterparts, which likely contribute to the phenotypic characteristics of MF. Furthermore, differentially methylated CpG sites in ASXL1 mutated MF cases are found in regulatory regions that could be associated with aberrant gene expression of ASXL1 target genes.

Original languageEnglish
Article number6774
JournalScientific Reports
Volume7
Number of pages11
ISSN2045-2322
DOIs
Publication statusPublished - 28 Jul 2017

    Research areas

  • CHRONIC MYELOMONOCYTIC LEUKEMIA, POLYCOMB REPRESSIVE COMPLEX, MYELOPROLIFERATIVE NEOPLASMS, POLYCYTHEMIA-VERA, ESSENTIAL THROMBOCYTHEMIA, MYELODYSPLASTIC SYNDROMES, H2A UBIQUITYLATION, PROFILING REVEALS, DISORDERS, DNMT3A

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