Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance

Abstract

One of the most important forms of drug resistance in acute myeloid leukemia is the multidrug resistance (MDR) phenotype, which is characterized by the expression of the MDR1 gene product, P-glycoprotein. Although a number of factors affect MDR1 gene expression, the genetic events that 'switch on' the human MDR1 gene in tumor cells that were previously P-glycoprotein negative have remained elusive. Here, we report evidence that the methylation status of the human MDR1 promoter may serve as a basis for this 'switch.' Based on Southern analysis using methylation-sensitive and methylation- insensitive restriction enzymes, a tight correlation was found between MDR phenotype and demethylation of ..