Expression of the multiple drug resistance gene (mdr‐1) and epitope masking in chronic lymphatic leukaemia

Abstract

Summary Resistance to cytotoxic agents is a common clinical problem in the treatment of chronic lymphatic leukaemia (CLL). The multidrug resistant (MDR) phenotype characterized by increased levels of a specific cell membrane p‐glycoprotein. confers cross resistance to a wide range of structurally dissimilar antineoplastic drugs. We have studied the expression of this p‐glycoprotein in chronic lymphatic leukaemia measured by immunofluorescence using a monoclonal antibody MRK 16 by flow cytometry. Initial results showed that only 12% of lymphocyte samples from CLL patients showed increased p‐glycoprotein, conflicting with a previous observation that 53% of CLL patients had an increased level of mdr‐1 mRNA. Treatment of the cells with neuraminidase to remove sialic acid residues increased the proportion of patients showing increased p‐glycoprotein to 52%. This suggests that in a subset of CLL patients post translational modification of the protein occurs masking the epitope recognized by MRK 16. Abnormal sialylation patterns associated with malignancy are a well‐recognized phenomenon.