Analysis of MDR1 and MDR3 Multidrug Resistance Gene Expression and Amplification in Consecutive Samples in Patients with Acute Lebkaemias

Abstract

White blood cells from a total of 19 patients diagnosed as having acute lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed (36 samples) for amplification and expression of the mdr1 and mdr3 genes. Nine of the patients had samples analysed at presentation and at subsequent stages of the disease (24 samples, including 4 at second relapse). Patients received standard MRC UK Trial remission-induction treatment protocols appropriate to disease and age. No amplification of either the mdr1 or mdr3 gene was found in any of the samples, and neither were mdr3 transcripts detected by dot-blot analysis using gene-specific probes. Transcripts of the mdr1 gene were found in only 2 ALL samples (of 10). However, mdr1 transcripts were detected in all AML patients and there was a significant increase in the transcript levels in these patients who went on to first and second relapse, compared with levels measured at presentation (P < 0.001). The results support the hypothesis that P-glycoprotein-mediated drug resistance may be a significant factor in tumour cell resistance to chemotherapy at relapse following initial induction-remission therapy for acute myeloid leukemia.

Multidrug resistance 1 gene expression and AgNOR in childhood acute leukemias

“…P-gp also prevents the entry of toxic metabolites into cells [2]. Notably, the MDR1 encoded protein actively expels many drugs used to treat leukemias such as anthracyclines, vinca alkaloids and epipodophyllotoxins [3], thus decreasing intracellular drug accumulation. P-glycoprotein mediated effl ux can be blocked by a number of chemo sensitizing agents such as verapamil, cyclosporin and quinine…”