{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:54:30Z","timestamp":1783814070769,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010408","name":"Polpharma Scientific Foundation","doi-asserted-by":"publisher","award":["GUMed\/K\/735\/12\/2018\/231"],"award-info":[{"award-number":["GUMed\/K\/735\/12\/2018\/231"]}],"id":[{"id":"10.13039\/501100010408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mastocytosis is a clinically heterogeneous, usually acquired disease of the mast cells with a survival time that depends on the onset of the disease and ranges from skin\u2010limited to systemic disease, including indolent and more aggressive variants. The crucial element in pathogenesis is the presence of oncogenic KIT somatic mutation D816V. Further epigenetic alterations are responsible for regulating the expression of genes. It is essential to identify indicators of disease progression, and the specific clinical picture to establish an appropriate therapeutic strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to analyze the relation of mastocytosis symptoms and epigenetic changes, and to identify epigenetic predictors of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Global DNA methylation profile analysis was performed in peripheral blood collected from 73 patients with indolent systemic mastocytosis (ISM) and 43\u00a0healthy adult volunteers. Levels of 5\u2010methylcytosine (5\u2010mC) and 5\u2010hydroxymethylcytosine (5\u2010hmC) were determined using an ELISA\u2010based method, while the methylation of the Alu and LINE\u20101 repeats were assayed with the quantitative methylation\u2010specific PCR technique. A questionnaire interview was conducted among the study participants to collect data on possible epigenetic modifiers. Additionally, the methylation profile was compared between three human mast cell lines: ROSA KIT D816V, ROSA KIT WT, and HMC\u20101.1 KIT V560G, in order to assess the association between <jats:italic>KIT<\/jats:italic> mutations and methylation profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significantly lower level of DNA hydroxymethylation (5\u2010hmC) in the blood was found in patients with ISM as compared to the controls (0.022% vs. 0.042%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0001). Differences in the markers of global DNA methylation (5\u2010mC, Alu, LINE\u20101) were not statistically significant, although they did indicate generally higher DNA methylation in patients with mastocytosis. The 5\u2010hmC level was significantly associated with allergy (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.011) in patients with ISM, showing a higher level of 5\u2010hmC in patients with allergy as compared to patients without allergy. The in vitro study revealed significant differences between the studied cell lines at the level of 5\u2010mC, Alu, and LINE\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study confirms that epigenetic changes are involved in mastocytosis, and suggests that allergy may be an important epigenetic modifier of the disease. A possible association between <jats:italic>KIT<\/jats:italic> mutations and methylation status observed in human mast cell lines requires further investigation in human studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Implications<\/jats:title><jats:p>Epigenetic alterations are involved in mastocytosis pathology. The possible role of allergy as an important epigenetic modifier suggests the more impaired function of mast cells in ISM patients without allergy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Capsule summary<\/jats:title><jats:p>Decreased DNA demethylation in the blood DNA of patients with ISM confirms that epigenetic alterations are involved in mastocytosis pathology. We observed a possible role of allergy as an important epigenetic modifier. There is a possible association between KIT mutations and the methylation status observed in human mast cell lines.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.12074","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T09:57:22Z","timestamp":1635847042000},"source":"Crossref","is-referenced-by-count":7,"title":["DNA methylation profile in patients with indolent systemic mastocytosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-1555","authenticated-orcid":false,"given":"Aleksandra","family":"G\u00f3rska","sequence":"first","affiliation":[{"name":"Department of Allergology Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Jab\u0142o\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Translational Research Nofer Institute of Occupational Medicine  Lodz 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