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

Br J Haematol. 1990 Oct;76(2):226-30. doi: 10.1111/j.1365-2141.1990.tb07876.x.

Abstract

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 suggest 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal
  • Antigens, CD / analysis
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cell Line
  • Chlorambucil / therapeutic use
  • Drug Resistance / genetics*
  • Epitopes / analysis
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Membrane Glycoproteins / analysis*
  • Membrane Glycoproteins / genetics
  • Neuraminidase / pharmacology
  • Phenotype
  • RNA, Messenger / genetics
  • Reference Values
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Transcription, Genetic

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal
  • Antigens, CD
  • Epitopes
  • Membrane Glycoproteins
  • RNA, Messenger
  • Chlorambucil
  • Neuraminidase