{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:12:23Z","timestamp":1761919943465},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","award":["12C47"],"award-info":[{"award-number":["12C47"]}],"id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>As disruption of epigenetic control is a frequent event in solid tumors and leukemia, we investigated changes in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation (5<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content>) and hydroxymethylation (5hmC) in patients with systemic mastocytosis (<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>), a rare myeloproliferative disease with a wide spectrum of severity, characterized by the accumulation of mast cells in various organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured overall genomic levels of 5hmC and 5<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content> in patients with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> by dot blot, as well as by quantitative immunofluorescence in samples of cutaneous mastocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall 5hmC levels were reduced in all patients with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>, but to a greater extent in the presence of higher D816V mutational load in the <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic> oncogene, which affects prognosis and therapeutic options in these patients. Loss of 5hmC was likely due to systemic effects of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> as it did not correlate with overall mast cell burden in these patients, nor it was due to inactivating mutations of <jats:italic><jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>2<\/jats:italic> or reduced <jats:italic><jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>2<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The correlation between <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> diagnosis and significantly low 5hmC levels suggests that reduction of 5hmC represents a systemic effect of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> that may be useful for patient stratification and that measurements of 5hmC levels may serve as a better prognostic marker than <jats:italic><jats:styled-content 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