High multidrug resistance protein activity in acute myeloid leukaemias is associated with poor response to chemotherapy and reduced patient survival


O. Fardel, INSERM U456, Faculté de Pharmacie, 2 Avenue du Pr L. Bernard, 35043, Rennes, France. E-mail: olivier.fardel@univ-rennes1.fr


Summary.  Multidrug resistance protein (MRP) activity was investigated in 44 newly diagnosed acute myeloid leukaemia (AML) patients using a functional assay based on efflux of carboxy-2′,7′-dichlorofluorescein, an anionic dye handled by both MRP1 and MRP2. Elevated MRP transport was detected in 29% of cases, but was not significantly correlated with sex, age, white blood cell count at diagnosis or karyotype. In contrast, it was associated with secondary AML (P = 0·002), CD34 positivity (P = 0·041) and P-glycoprotein activity (P = 0·01). There was a lower rate of complete remission in MRP-positive patients versus MRP-negative patients (23% versus 81%; P = 0·001); overall survival was also better for MRP-negative patients (P = 0·004). These data indicate a probable role for MRP activity in the clinical outcome of AML.