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MDR1 gene expression and drug resistance of AML cells

J M Nørgaard1, A Bukh, S T Langkjer

  • 1Department of Medicine and Haematology, Aarhus University Hospital, Denmark.

British Journal of Haematology
|March 21, 1998
PubMed

Insights

Cellular drug resistance in acute myeloid leukemia (AML) varies by drug. Multiple drug resistance 1 (MDR1) gene expression impacts resistance to certain drugs like daunorubicin, doxorubicin, and etoposide, but not aclarubicin.

Area of Science:

  • Hematology
  • Pharmacology
  • Molecular Biology

Background:

  • Acute myeloid leukemia (AML) treatment efficacy can be limited by cellular drug resistance.
  • The multiple drug resistance 1 (MDR1) gene is implicated in chemoresistance in various cancers.
  • Understanding drug resistance mechanisms is crucial for optimizing AML therapy.

Purpose of the Study:

  • To investigate cellular drug resistance to six chemotherapy agents in acute myeloid leukemia (AML) at disease presentation.
  • To determine the correlation between MDR1 gene expression and drug resistance in AML cells.
  • To analyze cross-activities among tested drugs to inform potential therapeutic strategies.

Main Methods:

  • Utilized the MTT assay to assess cellular drug resistance in 93 AML cases.
  • Investigated MDR1 gene expression in 31 AML cases using semi-quantitative competitive RT-PCR.
  • Analyzed correlations between MDR1 expression, drug resistance, and drug cross-activities.

Main Results:

  • Drug resistance to daunorubicin, doxorubicin, and etoposide correlated with MDR1 expression in AML cells.
  • Aclarubicin resistance was independent of MDR1 expression levels.
  • Distinct cross-activity patterns were observed: high cross-activity among daunorubicin, doxorubicin, etoposide, and mitoxantrone; moderate for cytosine arabinoside; and absent to moderate for aclarubicin.

Conclusions:

  • MDR1 gene expression significantly influences cellular drug resistance to specific agents in AML.
  • Aclarubicin's resistance mechanism is not dependent on MDR1, suggesting its potential utility.
  • Aclarubicin may serve as an alternative to MDR1-related drugs, provided its efficacy is comparable.

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