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

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Epigenetic changes in myelofibrosis : Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations. / Myrtue Nielsen, Helene; Lykkegaard Andersen, Christen; Westman, Maj; Sommer Kristensen, Lasse; Asmar, Fazila; Arvid Kruse, Torben; Thomassen, Mads; Stauffer Larsen, Thomas; Skov, Vibe; Lotte Hansen, Lise; Weis Bjerrum, Ole; Hasselbalch, Hans Carl; Punj, Vasu; Grønbæk, Kirsten.

In: Scientific Reports, Vol. 7, 6774, 2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Myrtue Nielsen, H, Lykkegaard Andersen, C, Westman, M, Sommer Kristensen, L, Asmar, F, Arvid Kruse, T, Thomassen, M, Stauffer Larsen, T, Skov, V, Lotte Hansen, L, Weis Bjerrum, O, Hasselbalch, HC, Punj, V & Grønbæk, K 2017, 'Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations', Scientific Reports, vol. 7, 6774. https://doi.org/10.1038/s41598-017-07057-3

APA

Myrtue Nielsen, H., Lykkegaard Andersen, C., Westman, M., Sommer Kristensen, L., Asmar, F., Arvid Kruse, T., Thomassen, M., Stauffer Larsen, T., Skov, V., Lotte Hansen, L., Weis Bjerrum, O., Hasselbalch, H. C., Punj, V., & Grønbæk, K. (2017). Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations. Scientific Reports, 7, [6774]. https://doi.org/10.1038/s41598-017-07057-3

Vancouver

Myrtue Nielsen H, Lykkegaard Andersen C, Westman M, Sommer Kristensen L, Asmar F, Arvid Kruse T et al. Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations. Scientific Reports. 2017;7. 6774. https://doi.org/10.1038/s41598-017-07057-3

Author

Myrtue Nielsen, Helene ; Lykkegaard Andersen, Christen ; Westman, Maj ; Sommer Kristensen, Lasse ; Asmar, Fazila ; Arvid Kruse, Torben ; Thomassen, Mads ; Stauffer Larsen, Thomas ; Skov, Vibe ; Lotte Hansen, Lise ; Weis Bjerrum, Ole ; Hasselbalch, Hans Carl ; Punj, Vasu ; Grønbæk, Kirsten. / Epigenetic changes in myelofibrosis : Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations. In: Scientific Reports. 2017 ; Vol. 7.

Bibtex

@article{a52629bff7f34c938a65d1b604ed7cf9,
title = "Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations",
abstract = "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.",
keywords = "Journal Article",
author = "{Myrtue Nielsen}, Helene and {Lykkegaard Andersen}, Christen and Maj Westman and {Sommer Kristensen}, Lasse and Fazila Asmar and {Arvid Kruse}, Torben and Mads Thomassen and {Stauffer Larsen}, Thomas and Vibe Skov and {Lotte Hansen}, Lise and {Weis Bjerrum}, Ole and Hasselbalch, {Hans Carl} and Vasu Punj and Kirsten Gr{\o}nb{\ae}k",
year = "2017",
doi = "10.1038/s41598-017-07057-3",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Epigenetic changes in myelofibrosis

T2 - Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations

AU - Myrtue Nielsen, Helene

AU - Lykkegaard Andersen, Christen

AU - Westman, Maj

AU - Sommer Kristensen, Lasse

AU - Asmar, Fazila

AU - Arvid Kruse, Torben

AU - Thomassen, Mads

AU - Stauffer Larsen, Thomas

AU - Skov, Vibe

AU - Lotte Hansen, Lise

AU - Weis Bjerrum, Ole

AU - Hasselbalch, Hans Carl

AU - Punj, Vasu

AU - Grønbæk, Kirsten

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41598-017-07057-3

DO - 10.1038/s41598-017-07057-3

M3 - Journal article

C2 - 28754985

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 6774

ER -

ID: 185180638