The multidrug resistance in human leukemias. Minireview

Related Experiment Video

Updated: Oct 28, 2026

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

O Zubercová1, O Babusíková

  • 1Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.

Neoplasma
|August 4, 1998
PubMed

Insights

Multidrug resistance (MDR) in leukemia/lymphoma is linked to P-glycoprotein (P-gp) expression. This resistance, mediated by the mdr1 gene, can be overcome by specific non-cytotoxic drugs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Clinically refractory leukemia and lymphoma often overexpress P-glycoprotein (P-gp).
  • P-gp is encoded by the multidrug resistance (MDR) gene, mdr1.
  • MDR confers resistance to various lipophilic chemotherapy drugs.

Purpose of the Study:

  • To investigate the role of P-gp in multidrug resistance.
  • To explore methods for circumventing P-gp mediated drug efflux.

Main Methods:

  • Utilized cell lines expressing the mdr1 gene.
  • Assessed drug resistance to anthracyclines, vinca alkaloids, and epopodophyllotoxins.
  • Employed mdr1 cDNA transfer to confer resistance.
  • Measured P-gp activity using the rhodamine 123 fluorescence probe.
  • Evaluated the effect of verapamil and cyclosporin A on drug resistance.

Main Results:

  • mdr1-expressing cells demonstrated resistance to multiple structurally unrelated drugs.
  • MDR phenotype was transferable via mdr1 cDNA.
  • Resistant cells showed increased P-gp overexpression and enhanced efflux of rhodamine 123.
  • Verapamil and cyclosporin A effectively circumvented P-gp mediated drug efflux.

Conclusions:

  • P-glycoprotein (P-gp) is a key mediator of multidrug resistance (MDR) in leukemia and lymphoma.
  • The mdr1 gene product, P-gp, drives drug efflux and therapeutic refractoriness.
  • Non-cytotoxic drugs like verapamil and cyclosporin A show potential for overcoming MDR.

More Related Videos

Modeling Chemotherapy Resistant Leukemia In Vitro08:41

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...