MDR1, MRP1 and LRP expression in patients with untreated acute leukaemia: Correlation with 99mTc-MIBI bone marrow scintigraphy

Abstract

Chemotherapy failure linked to multidrug-resistance (MDR) plays an important role in many cancer types, including leukaemia. It is believed that overexpression of some of membrane or intracellular proteins confers the MDR phenotype to cancer cells. (99m)Tc-sestamibi (MIBI) is a transport substrate for the Pgp pump. We assessed the bone marrow uptake of (99m)Tc-MIBI and its correlation with messenger RNA (mRNA) levels of MDR1, multidrug-resistance associated protein-1 (MRP1) and lung resistance protein (LRP) in acute leukaemia. A total of 26 patients (age range 17-72 years; mean age 51.88+/-2.52 years) with newly diagnosed acute leukaemia were included in the study. The expression of MDR1, MRP1 and LRP on mRNA levels were assessed by quantitative RT-PCR in the blast cells. The MIBI uptake in the bone marrow was evaluated using a quantitative scoring system with determination of the tumour-to-background ratios for the bone marrow areas. The correlation between the quantitative RT-PCR results and MIBI uptake was analysed by using Spearman's rank correlation coefficients with two-tailed test of significance. There was an inverse relationship between (99m)Tc-MIBI uptake of bone marrow and both mRNA levels of MDR1 and MRP1 (P=0.000, r= -0.733 and P=0.001, r= -0.610, respectively). No correlation was found between MIBI uptake and mRNA levels of LRP. Increased expression of MDR1 and MRP1 correlates with a low accumulation of (99m)Tc-MIBI in bone marrow areas in patients with acute leukaemia. (99m)Tc-MIBI bone marrow scintigraphy can identify the MDR1 and MRP1 phenotype, but not LRP, in patients with acute leukaemia.