{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:28:16Z","timestamp":1753878496736,"version":"3.41.2"},"reference-count":13,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The histone deacetylase inhibitor (HDACI) valproic acid has been shown to inhibit the growth of multiple paediatric tumour types and is well tolerated in a childhood cancer setting. The current study was designed to develop a novel imaging flow cytometry method for the detection of histone H4 acetylation in white blood cells obtained from childhood cancer patients treated with valproic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>HL\u201060 cells and whole blood samples from healthy volunteers were incubated with valproic acid (0\u20108\u00a0mM) for 0\u201024\u00a0hours, with additional blood samples collected from ependymoma patients receiving valproic acid on the SIOP Ependymoma II clinical trial. An imaging flow cytometry method was developed using an ImageStream<jats:sup>\u00ae\u03c7<\/jats:sup> flow cytometer, collecting 100\u00a0000 images per sample following excitation of PE tagged acH4 antibody and DAPI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean percentage of acH4\u2010positive cells increased to a greater extent than increases in mean and median fluorescence intensity following incubation with valproic acid. Comparable results were observed for in vitro and ex vivo experiments, and the assay was shown to be appropriate for clinical sample analysis. Myeloid cells exhibited a smaller proportion of acH4\u2010positive cells than the lymphoid population, but a greater fold increase above basal levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The percentage of acH4\u2010positive myeloid cells has the potential to be used as a robust pharmacodynamic biomarker for the measurement of acH4 for HDACIs. The developed assay is now being utilised in a clinical trial involving the treatment of childhood ependymoma patients with valproic acid.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13115","type":"journal-article","created":{"date-parts":[[2019,3,31]],"date-time":"2019-03-31T09:41:30Z","timestamp":1554025290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel imaging flow cytometry method for the detection of histone H4 acetylation in myeloid cells"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3943-4896","authenticated-orcid":false,"given":"Suriyon","family":"Uitrakul","sequence":"first","affiliation":[{"name":"Newcastle Cancer Centre Pharmacology Group Northern Institute for Cancer Research, Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Hutton","sequence":"additional","affiliation":[{"name":"Newcastle Cancer Centre Pharmacology Group Northern Institute for Cancer Research, Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-8678","authenticated-orcid":false,"given":"Gareth J.","family":"Veal","sequence":"additional","affiliation":[{"name":"Newcastle Cancer Centre Pharmacology Group Northern Institute for Cancer Research, Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-6713","authenticated-orcid":false,"given":"David","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Newcastle Cancer Centre Pharmacology Group Northern Institute for Cancer Research, Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-0324"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2133"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35106079"},{"key":"e_1_2_7_5_1","first-page":"597","volume-title":"Chapter 37\u2010Clinical Applications of Histone Deacetylase Inhibitors A2\u2010Tollefsbol, Trygve. 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