Establishment of Multi-Drug Resistance Functional Assay and Correlation of Multi-Drug Resistance Activity and Chemotherapeutic Outcomes in Patients with Acute Leukemia / 대한혈액학회지

ABSTRACT

BACKGROUND: Multi-drug resistance (MDR) is one of the most important obstacles in the chemotherapy of acute leukemia, so the modulators of MDR have been developed and tried. METHODS: We measured MDR function and expressoin (surface and cytoplasmic p-glycoprotein and cytoplasmic multidrug-resistance associated protein (MRP)) and inhibitory effects of MDR modulators (cyclosporine and verapamil) by flow cytometry with MDR positive cell line and bone marrow aspirates of patients with acute leukemia (128 specimen). We compared these methods, and tried to clarify the effects of MDR on chemotherapy in patients with acute leukemia. RESULTS: The MDR functional assay and the detection method for inhibitory effects of MDR modulators (cyclosporine and verapamil) by flow cytometry using rhodamine 123 were established. These MDR functional assay was more sensitive, accurate, relatively simple and very economic, compared with the immunofluorescence assays of surface and cytopla-smic p-glycoprotein and cytoplasmic MRP. The positivity of MDR functional assay was observed in about 60% of patients with acute leukemia, and MDR activity (%) was inversely correlated with the complete remission rate and mean survival time. About 60% of the patients showing positive MDR activity revealed MDR inhibitory responses by cyclosporine and/or verapamil, especially all cases of acute myeloid leukemia in persistence after chemotherapy showed MDR inhibitory effect of cyclosporine. CONCLUSION: The chemotherapeutic out- comes of acute leukemia can be expected by MDR functional assay. And it is possible to overcome MDR by the administration of MDR modulator selected according to the results of the functional assay for MDR inhibitory effect in acute leukemia patients with MDR positivity.