Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status

J Cancer Res Clin Oncol. 2010 Mar;136(3):403-10. doi: 10.1007/s00432-009-0670-9. Epub 2009 Sep 1.

Abstract

Purpose: To assess whether the poor prognosis of ZAP70-positive B-cell chronic lymphocytic leukemia (CLL) is associated with the overexpression of ABC transporter genes that are responsible for pleiotropic drug resistance.

Materials and methods: The transcript level of ten drug transporters was analyzed using semiquantitative and quantitative RT-PCR in control hematopoietic cells, in 41 CLL patient samples and in 5 lymphoma cell lines. ZAP70 status was determined by immunoblotting.

Results: Of all analyzed transporters, MDR1, MDR2, MRP1, MRP4, MRP5, and MRP7 were expressed at a significantly higher level in B lymphocytes when compared with other hematopoietic cells in peripheral blood. A subgroup of 41 CLL patient samples showed similar or higher expression of these genes than control B cells, and CLL cells exhibited high expression when compared with multiple lymphoma cell lines. No significant correlation between ZAP70 expression and ABC transporter expression was observed.

Conclusion: The ZAP70 status is independent of the multidrug resistance phenotype in CLL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Cells / metabolism
  • Blood Cells / pathology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Lymphoma, Non-Hodgkin / genetics
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Phenotype
  • Tumor Cells, Cultured
  • ZAP-70 Protein-Tyrosine Kinase / genetics*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / physiology*

Substances

  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human