Effects of Ibrutinib on Proliferation and Histamine Release in Canine Neoplastic Mast Cells
Overview
Veterinary Medicine
Authors
Affiliations
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is effective in the treatment of human chronic lymphocytic leukaemia and mantle cell lymphoma. Recent data have shown that ibrutinib also blocks IgE-dependent 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-1 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 values ranging between 0.1 and 1 μM in primary MCT cells and between 1 and 3 μM in C2 and NI-1 cells. In C2 cells, the combination "ibrutinib + midostaurin" produced synergistic growth-inhibitory effects. At higher concentrations, ibrutinib also induced apoptosis in both MC lines. Finally, ibrutinib was found to suppress IgE-dependent histamine release in primary MCT cells, with IC values ranging from 0.05 to 0.1 μM in NI-1 cells, and from 0.05 to 1 μM in primary MCT cells. In summary, ibrutinib exerts anti-proliferative effects in canine neoplastic MCs and counteracts IgE-dependent 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.
Heparin suppresses FoxO1/pFoxO1 signaling axis in vascular smooth muscle cells.
Shokri N, Elahimanesh M, Bakhshandeh M, Najafi M Biochem Biophys Rep. 2025; 41:101954.
PMID: 40046255 PMC: 11880713. DOI: 10.1016/j.bbrep.2025.101954.
NF-kB affects migration of vascular smooth muscle cells after treatment with heparin and ibrutinib.
Shokri N, Ghasempour G, Soleimani A, Elahimanesh M, Najafi M Biochem Biophys Rep. 2024; 38:101685.
PMID: 38524279 PMC: 10957380. DOI: 10.1016/j.bbrep.2024.101685.
Bruton's tyrosine kinase inhibition for the treatment of allergic disorders.
Lin E, Suresh R, Dispenza M Ann Allergy Asthma Immunol. 2024; 133(1):33-42.
PMID: 38492772 PMC: 11222055. DOI: 10.1016/j.anai.2024.03.002.
Potential Role of Moesin in Regulating Mast Cell Secretion.
Theoharides T, Kempuraj D Int J Mol Sci. 2023; 24(15).
PMID: 37569454 PMC: 10418457. DOI: 10.3390/ijms241512081.
Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing.
Burchett J, Dailey J, Kee S, Pryor D, Kotha A, Kankaria R Cells. 2022; 11(19).
PMID: 36230993 PMC: 9564111. DOI: 10.3390/cells11193031.