Are MTT assays the right tool to analyze drug resistance caused by ABC-transporters in patient samples?

Drug resistance can be caused by ATP-binding-cassette (ABC)-transporters which function as outward pumps for chemotherapeutic drugs. The aim of the present study was to analyze the association between eight ABC-transporters (BCRP, MDR1, SMRP, MRP1, MRP2, MRP3, MRP4, and MRP5) and in vitro drug resistance. Leukemic cells from 52 children with previously untreated acute leukemia (ALL: n=37; AML: n=15) were analysed. The expression of the ABC-transporters was measured by TaqMan real-time PCR. In vitro drug resistance to cytarabine, vincristine, tioguanine, daunorubicin, etoposide, dexamethasone, and prednisone was analysed with methyl-thiazol-tetrazolium (MTT) assays.MDR1 was weakly associated with resistance to vincristine (p<0.05) in AML samples. No other correlation between an ABC-transporter and a higher in vitro drug resistance was found. In vitro drug resistance was not associated with the simultaneous expression of a larger number of ABC-transporters.MTT assays are a widely used and validated method to analyse in vitro drug resistance but they may not be a useful tool to detect resistance which is caused by drug efflux in patient samples. If that is the case, MTT assays and the expression of ABC-transporters could provide complementary information on the drug resistance profile of patients with acute leukemia.