Breast cancer resistance protein expression and resistance to daunorubicinin blast cells from patients with acute myeloid leukaemia

Breast cancer resistance protein (BCRP) is a recently described member of t he ATP binding cassette transporter superfamily. It has been shown to confe r resistance to mitoxantrone, topotecan, doxorubicin and daunorubicin in hu man tumour cell lines. We describe a study of BCRP expression in blast cell s derived from 20 patients with acute myeloid leukaemia (AML). Twelve sampl es were from patients who had received previous cytotoxic therapy, BCRP exp ression was measured by immunocytochemistry using the BXP-34 monoclonal ant ibody. In vitro drug sensitivity was assessed using the methyl thiazol tetr azoliumbromide assay. BCRP expression varied between patients, and six out of 22 (27%) samples had >10% cells staining positively (median 37%, range 1 3-95%). BCRP positivity was seen in both de novo samples and those from pre viously treated patients. There was a marked variation in the effect of all drugs tested between patients. Although there was no correlation between B CRP positivity and the effect of mitoxantrone, topotecan or doxorubicin, th e median daunorubicin LC50 value of BCRP+ cells was fourfold higher than th at of BCRP- cells (0.89 mu mol/l compared with 0.21 mu mol/l, P<0.05). Thes e results suggest that BCRP may be involved in resistance to the agents com monly used in AML and may explain some of the anomalous results found when studying other membrane transporters, such as P-gp or MRP.