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Recent data have shown that ibrutinib also blocks IgE\u2010dependent activation and histamine release in human basophils (BAs) and mast cells (MCs). The aim of this study was to investigate whether BTK serves as a novel therapeutic target in canine mast cell tumours (MCTs). We evaluated the effects of ibrutinib on two canine MC lines, C2 and NI\u20101 and on primary MCs obtained from canine MCTs (n = 3). Using flow cytometry, we found that ibrutinib suppresses phosphorylation of BTK and of downstream STAT5 in both MC lines. In addition, ibrutinib decreased proliferation of neoplastic MCs, with IC<jats:sub>50<\/jats:sub> values ranging between 0.1 and 1 \u03bcM in primary MCT cells and between 1 and 3 \u03bcM in C2 and NI\u20101 cells. In C2 cells, the combination \u201cibrutinib + midostaurin\u201d produced synergistic growth\u2010inhibitory effects. At higher concentrations, ibrutinib also induced apoptosis in both MC lines. Finally, ibrutinib was found to suppress IgE\u2010dependent histamine release in primary MCT cells, with IC<jats:sub>50<\/jats:sub> values ranging from 0.05 to 0.1 \u03bcM in NI\u20101 cells, and from 0.05 to 1 \u03bcM in primary MCT cells. In summary, ibrutinib exerts anti\u2010proliferative effects in canine neoplastic MCs and counteracts IgE\u2010dependent histamine release in these cells. Based on our data, ibrutinib may be considered as a novel therapeutic agent for the treatment of canine MCT. The value of BTK inhibition in canine MCT patients remains to be elucidated in clinical trials.<\/jats:p>","DOI":"10.1111\/vco.12520","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T06:35:07Z","timestamp":1562654107000},"page":"553-561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effects of ibrutinib on proliferation and histamine release in canine neoplastic mast cells"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6509-2810","authenticated-orcid":false,"given":"Susanne","family":"Gamperl","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Division of Hematology &amp; Hemostaseology Medical University of Vienna  Vienna 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