{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:16:16Z","timestamp":1792444576472,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T00:00:00Z","timestamp":1256083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> KIT tyrosine kinase inhibitors (TKI), such as nilotinib or midostaurin (PKC412), are increasingly used in clinical trials to counteract neoplastic cell growth in patients with aggressive mast cell (MC) disorders. However, these patients suffer not only from MC infiltration and consecutive organ damage but also from MC mediator\u2010related symptoms.<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> We examined the effects of three KIT TKI, imatinib, nilotinib, and midostaurin, on IgE\u2010dependent mediator release in normal human blood basophils and cultured cord blood cell\u2010derived MC, and on spontaneous histamine secretion in the MC leukaemia cell line HMC\u20101 and the basophil cell line KU812.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> The multi\u2010kinase inhibitor midostaurin that interacts with KIT and protein kinase C was found to counteract anti\u2010IgE\u2010induced mediator release in blood basophils and cultured cord blood cell\u2010derived MC in all samples examined. By contrast, no effects of imatinib or nilotinib on histamine secretion in basophils or MC were found. The effects of midostaurin on histamine release were dose\u2010dependent and occurred at pharmacologic concentrations (IC<jats:sub>50<\/jats:sub> 10\u2010100\u2003n<jats:sc>m<\/jats:sc>). Midostaurin was also found to inhibit the IgE\u2010dependent up\u2010regulation of CD63 on cultured cord blood cell\u2010derived human MC, but did not inhibit IgE\u2010dependent up\u2010regulation of CD63 or CD203c in human blood basophils.<\/jats:p><jats:p><jats:bold>Conclusion\n\t\t\t\t\t<\/jats:bold> Midostaurin may be a beneficial drug in aggressive systemic mastocytosis not only because of its growth\u2010inhibitory effects but also because of its additional effects on activation and mediator release in MC and basophils.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2009.03353.x","type":"journal-article","created":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T07:40:34Z","timestamp":1256110834000},"page":"1711-1720","source":"Crossref","is-referenced-by-count":79,"title":["Midostaurin (PKC412) inhibits immunoglobulin E\u2010dependent activation and mediator release in human blood basophils and mast cells"],"prefix":"10.1111","volume":"39","author":[{"given":"M.\u2010T.","family":"Krauth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Mirkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Baumgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kneidinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Valent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,10,21]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"695","article-title":"Diagnosis and treatment of systemic 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