C-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571)

Purpose: In order to determine whether Ewing tumour patients may be potential candidates for imatinib mesylate therapy, we analysed the expression of the currently known imatinib mesylate-sensitive tyrosine kinases and tested sensitivity to imatinib mesylate in a panel of eight Ewing tumour cell lines in vitro. Methods: Expression of the di1erent tyrosine kinases was assessed by flow cytometry and RT-PCR. Sensitivity to imatinib mesylate was analysed using a standard MTT proliferation assay. Results: Flow cytometric and RT-PCR analyses in a panel of eight Ewing tumour cell lines demonstrated expression of several imatinib mesylate-sensitive tyrosine kinases, including c-KIT, platelet-derived growth factor receptor, c-ABL and c-ARG. However, in the MTT proliferation assay, all eight Ewing tumour cell lines were found to be resistant to imatinib mesylate at concentrations ranging from 0.1 to 10 μM. Conclusions: Despite the expression of imatinib mesylate-sensitive tyrosine kinases, Ewing tumour cells proved resistant to imatinib mesylate in vitro. This observation has implications for the selection of patients for experimental therapy with imatinib mesylate.