Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells

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T Tsuruo1, Y Sugimoto, H Hamada

  • 1Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.

Insights

P-glycoprotein expression in leukemia cells can predict treatment resistance. Detecting this protein using a monoclonal antibody (MRK16) and mdr1 mRNA levels may help forecast refractory cancer states.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • P-glycoprotein is a key efflux pump involved in multidrug resistance (MDR).
  • Overexpression of P-glycoprotein in cancer cells can lead to therapeutic failure.
  • Chronic myelogenous leukemia (CML) can develop resistance to standard treatments.

Purpose of the Study:

  • To investigate P-glycoprotein expression in clinical samples of chronic myelogenous leukemia.
  • To correlate P-glycoprotein levels with treatment refractoriness in CML patients.

Main Methods:

  • Utilized a monoclonal antibody (MRK16) to detect P-glycoprotein expression.
  • Analyzed mdr1 mRNA levels, which encode P-glycoprotein.
  • Examined clinical leukemic cell samples from patients with CML in blast crisis.

Main Results:

  • P-glycoprotein expression was detected in leukemia cells from 3 out of 6 patients with CML blast crisis.
  • These reactive cell samples showed high levels of mdr1 mRNA.
  • A correlation between P-glycoprotein expression and clinical refractoriness was observed.

Conclusions:

  • P-glycoprotein expression, detectable by MRK16 antibody, is present in a subset of CML blast crisis patients.
  • High mdr1 mRNA levels accompany P-glycoprotein overexpression in these resistant cells.
  • Assessing P-glycoprotein and mdr1 mRNA may aid in predicting the refractory state of CML, guiding therapeutic strategies.

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