Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia

We have used a combination of flow cytometric assays to define multidrug re sistance (MDR) positive and negative blasts in cryopreserved samples from 4 7 MRC trial patients with acute myeloblastic leukaemia (AML). Our primary t est is a standardized assay for daunorubicin accumulation. Confirmatory ass ays for MDR comprised the cyclosporin modulation assay for rhodamine-123 up take as a measure of functional P-glycoprotein and the measurement of lung resistance protein and multidrug resistance associated protein (with LRP-56 and MRPr1 respectively). 57% of samples had both low accumulation and at l east one positive confirmatory test. 32% were MDR negative in all four assa ys. 15% of patients had primary chemo-resistant disease. Resistant disease rates were 22% for confirmed. MDR-positive patients and 0% for confirmed MD R-negative patients (P=0.07). Complete remission was achieved in 74% of pat ients, with rates of 63% in confirmed MDR-positive patients and 93% in conf irmed MDR-negative patients (P=0.06). The use of a standardized method for daunorubicin uptake, combined with the use of confirmatory tests, should re duce the uncertainty that is currently characteristic of MDR evaluation in leukaemia. In comparison with daunorubicin uptake, p-gp expression, measure d using MRK-16 antibody, was more closely associated with remission rates ( P=0.01). This suggests an additional role for p-glycoprotein in mediating d rug resistance beyond that of a drug efflux pump.