Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat. / McPherson, Suzanne; Greenfield, Graeme; Andersen, Christen; Grinfeld, Jacob; Hasselbalch, Hans C.; Nangalia, Jyoti; Mills, Ken I.; McMullin, Mary F.

I: Experimental Hematology, Bind 79, 2019, s. 26-34.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

McPherson, S, Greenfield, G, Andersen, C, Grinfeld, J, Hasselbalch, HC, Nangalia, J, Mills, KI & McMullin, MF 2019, 'Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat', Experimental Hematology, bind 79, s. 26-34. https://doi.org/10.1016/j.exphem.2019.09.025

APA

McPherson, S., Greenfield, G., Andersen, C., Grinfeld, J., Hasselbalch, H. C., Nangalia, J., Mills, K. I., & McMullin, M. F. (2019). Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat. Experimental Hematology, 79, 26-34. https://doi.org/10.1016/j.exphem.2019.09.025

Vancouver

McPherson S, Greenfield G, Andersen C, Grinfeld J, Hasselbalch HC, Nangalia J o.a. Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat. Experimental Hematology. 2019;79:26-34. https://doi.org/10.1016/j.exphem.2019.09.025

Author

McPherson, Suzanne ; Greenfield, Graeme ; Andersen, Christen ; Grinfeld, Jacob ; Hasselbalch, Hans C. ; Nangalia, Jyoti ; Mills, Ken I. ; McMullin, Mary F. / Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat. I: Experimental Hematology. 2019 ; Bind 79. s. 26-34.

Bibtex

@article{7919a3826f584454a612d6e0fe5ce4ad,
title = "Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat",
abstract = "The myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal neoplastic disorders. Driver mutations in JAK2, CALR, and MPL genes have been identified in the majority of cases. Alongside these, an increasing number of genes are repeatedly identified as mutated in MPN. These, including ASXL1, TET2, DMNT3A, and EZH2, have key roles in epigenetic regulation. Dysregulation of epigenetic processes is therefore a key feature of MPN. Vorinostat is a pan histone deacetylase inhibitor (HDACi) that has been investigated in MPN. DNA methylation (DNAm) is a well-defined epigenetic mechanism of transcription modification. It is known to be affected by ageing, lifestyle, and disease. Epigenetic ageing signatures have been previously described allowing calculation of a methylation age (MA). In this study we examined the effect of vorinostat on MA in MPN cell lines and in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET) treated with vorinostat as part of a clinical trial. An older MA was observed in patients with a higher JAK2 V617F allele burden and those with a longer duration of disease. PV patients had a MA older than that predicted whilst MA was younger than predicted in ET. Treatment with vorinostat resulted in a younger MA in PV patients and older MA in ET patients, in both cases a trend towards the normal chronological age. When MA change was compared against response, nonresponse was associated with a younger than predicted MA in ET patients and a higher than predicted MA in PV patients. The link between MA and JAK2 mutant allele burden implies that allele burden has a role not only in clinical phenotype and disease evolution in MPN patients, but also in the overall methylation landscape of the mutated cells.",
author = "Suzanne McPherson and Graeme Greenfield and Christen Andersen and Jacob Grinfeld and Hasselbalch, {Hans C.} and Jyoti Nangalia and Mills, {Ken I.} and McMullin, {Mary F.}",
year = "2019",
doi = "10.1016/j.exphem.2019.09.025",
language = "English",
volume = "79",
pages = "26--34",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Methylation age as a correlate for allele burden, disease status, and clinical response in myeloproliferative neoplasm patients treated with vorinostat

AU - McPherson, Suzanne

AU - Greenfield, Graeme

AU - Andersen, Christen

AU - Grinfeld, Jacob

AU - Hasselbalch, Hans C.

AU - Nangalia, Jyoti

AU - Mills, Ken I.

AU - McMullin, Mary F.

PY - 2019

Y1 - 2019

N2 - The myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal neoplastic disorders. Driver mutations in JAK2, CALR, and MPL genes have been identified in the majority of cases. Alongside these, an increasing number of genes are repeatedly identified as mutated in MPN. These, including ASXL1, TET2, DMNT3A, and EZH2, have key roles in epigenetic regulation. Dysregulation of epigenetic processes is therefore a key feature of MPN. Vorinostat is a pan histone deacetylase inhibitor (HDACi) that has been investigated in MPN. DNA methylation (DNAm) is a well-defined epigenetic mechanism of transcription modification. It is known to be affected by ageing, lifestyle, and disease. Epigenetic ageing signatures have been previously described allowing calculation of a methylation age (MA). In this study we examined the effect of vorinostat on MA in MPN cell lines and in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET) treated with vorinostat as part of a clinical trial. An older MA was observed in patients with a higher JAK2 V617F allele burden and those with a longer duration of disease. PV patients had a MA older than that predicted whilst MA was younger than predicted in ET. Treatment with vorinostat resulted in a younger MA in PV patients and older MA in ET patients, in both cases a trend towards the normal chronological age. When MA change was compared against response, nonresponse was associated with a younger than predicted MA in ET patients and a higher than predicted MA in PV patients. The link between MA and JAK2 mutant allele burden implies that allele burden has a role not only in clinical phenotype and disease evolution in MPN patients, but also in the overall methylation landscape of the mutated cells.

AB - The myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal neoplastic disorders. Driver mutations in JAK2, CALR, and MPL genes have been identified in the majority of cases. Alongside these, an increasing number of genes are repeatedly identified as mutated in MPN. These, including ASXL1, TET2, DMNT3A, and EZH2, have key roles in epigenetic regulation. Dysregulation of epigenetic processes is therefore a key feature of MPN. Vorinostat is a pan histone deacetylase inhibitor (HDACi) that has been investigated in MPN. DNA methylation (DNAm) is a well-defined epigenetic mechanism of transcription modification. It is known to be affected by ageing, lifestyle, and disease. Epigenetic ageing signatures have been previously described allowing calculation of a methylation age (MA). In this study we examined the effect of vorinostat on MA in MPN cell lines and in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET) treated with vorinostat as part of a clinical trial. An older MA was observed in patients with a higher JAK2 V617F allele burden and those with a longer duration of disease. PV patients had a MA older than that predicted whilst MA was younger than predicted in ET. Treatment with vorinostat resulted in a younger MA in PV patients and older MA in ET patients, in both cases a trend towards the normal chronological age. When MA change was compared against response, nonresponse was associated with a younger than predicted MA in ET patients and a higher than predicted MA in PV patients. The link between MA and JAK2 mutant allele burden implies that allele burden has a role not only in clinical phenotype and disease evolution in MPN patients, but also in the overall methylation landscape of the mutated cells.

U2 - 10.1016/j.exphem.2019.09.025

DO - 10.1016/j.exphem.2019.09.025

M3 - Journal article

C2 - 31563618

AN - SCOPUS:85074394752

VL - 79

SP - 26

EP - 34

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

ER -

ID: 238672037