Dasatinib (BMS354825) Inhibits IgE-Dependent Activation and Histamine Release in Human Blood Basophils.

Dasatinib (BMS354825) is a small molecule-type inhibitory drug that blocks several tyrosine kinases including PDGFR, KIT, BCR/ABL, and several src kinases. Dasatinib has recently been introduced as a new effective antileukemic drug in patients with imatinib-resistant chronic myeloid leukemia. However, because of the many targets of dasatinib and the broad range of potential target-cells in physiologic and pathologic tissues, dasatinib has recently been examined for its immunosuppressive and anti-inflammatory effects. We here report that dasatinib at 1 μM completely blocks the anti-IgE-induced release of histamine in human blood basophils in healthy subjects. The effects of dasatinib on histamine secretion in basophils were dose-dependent (IC₅₀: 50–100 nM). Dasatinib was also found to block recombinant allergen-induced release of histamine from human basophils in sensitized individuals. In addition, as assessed by flow cytometry, dasatinib (1 μM) was found to inhibit the IgE-dependent upregulation of several activation-linked antigens, including aminopeptidase N (CD13), LAMP-3 (CD63), endolyn (CD164), and the basophil-specific ectoenzyme E-NPP3 (CD203c) on the cell surface of human basophils. The effects of dasatinib on upregulation of basophil differentiation antigens were found to be dose-dependent and were seen in normal subjects as well as in allergic individuals. Together, these data show that dasatinib blocks IgE-mediated activation and histamine release in human blood basophils. These anti-allergic effects of dasatinib may have clinical implications and may point to additional indications for this multifunctional drug.