P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia

Despite treatment with intensive chemotherapy, a considerable number of patients with acute myeloid leukemia (AML) die from their disease due to the occurrence of resistance. Overexpression of the transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein (MRP) 1 has been identified as a major cause of cross-resistance to functionally and structurally unrelated drugs, In the present study, the functional activity of P-gp and MRP was determined in 104 de novo AML patients with a pow cytometric assay using rhodamine 123 (Rh123) in combination with PSC833 and carboxyfluorescein (CP) in combination with MK-571, The results were compared with clinical outcome and with known prognostic factors. The functional activity of P-gp and MRP, expressed as Rh123 efflux blocking by PSC833 and CF efflux blocking by MK-571, demonstrated a great variability in the AML patients. A strong negative correlation was observed between Rh123 efflux blocking by PSC833 and Rh123 accumulation (r(s) = -0.69, P <0.001) and between CP efflux blocking by MK-571 and CF accumulation (r(s) = -0.59, P