Intracellular P-gp contributes to functional drug efflux and resistance in acute myeloid leukaemia

Petranel Ferrao, Paul Sincock, Stephen Cole, Leonie Ashman

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Drug compartmentalization as well as drug efflux can contribute to drug resistance. We demonstrate the presence of P-gp in intracellular vesicles in certain AML cell lines and show localization of DNR to a similar subcellular compartment(s) that can be altered in the presence of P-gp inhibitors. Analysis of leukaemic cell lines and 50 AML patient samples showed that the level of P-gp mRNA or total P-gp protein correlated better with drug efflux than surface P-gp protein, suggesting that intracellular P-gp may contribute to MDR in AML. Therefore, the level of total P-gp protein or mRNA may be a better indicator of MDR than surface P-gp protein. In addition, we provide evidence for a novel mechanism of drug sequestration in K562 myeloid leukaemic cells.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalLeukemia Research
Volume25
Issue number5
DOIs
Publication statusPublished or Issued - 2001
Externally publishedYes

Keywords

  • AML
  • Drug efflux
  • Intracellular P-glycoprotein
  • Multidrug resistance

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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