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Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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P-Glycoprotein Expression in Drug-Resistant Chronic Lymphoproliferative Disorder.

G Majumdar1, A K Singh1

  • 1a Division of Haematology, United Medical and Dental School of Guy's and St Thomas', St Thomas' Campus, London, England.

Leukemia & Lymphoma
|July 28, 2016
PubMed
Summary

P-glycoprotein (P-gp) expression was studied in drug-resistant chronic lymphoproliferative disorders. P-gp was found in Adult T-cell leukemia/lymphoma and some prolymphocytic leukemia and chronic lymphocytic leukemia patients, suggesting a role in multidrug resistance.

Keywords:
P-Glycoproteinchronic lymphocytic leukaemialymphoproliferative disordersprolymphocytic leukaemia

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Chronic lymphoproliferative disorders (LPD) often exhibit drug resistance.
  • P-glycoprotein (P-gp) is a key mediator of multidrug resistance (MDR) in cancer cells.
  • Understanding P-gp expression in LPD is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To investigate the expression of P-glycoprotein (P-gp) in peripheral blood lymphocytes of patients with drug-resistant chronic lymphoproliferative disorders (LPD).
  • To determine the potential role of P-gp in mediating multidrug resistance in various subtypes of LPD.

Main Methods:

  • Direct immunofluorescence (IF) testing using monoclonal antibody (MoAb) C219 was employed.
  • Peripheral blood lymphocytes from 60 patients with drug-resistant LPD were analyzed.
  • Specific LPD subtypes included prolymphocytic leukemia (PLL), Adult T-cell leukemia/lymphoma (ATLL), hairy cell leukemia (HCL), and chronic lymphocytic leukemia (CLL).

Main Results:

  • P-gp expression was detected in 4/15 PLL patients and both ATLL patients.
  • None of the HCL patients expressed P-gp.
  • P-gp was found in 2/14 anthracycline-resistant CLL patients, but not in CLL patients resistant only to chlorambucil.
  • P-gp expression levels varied significantly (20-100%) among positive cases.
  • PMA stimulation did not induce P-gp in non-resistant CLL lymphocytes.

Conclusions:

  • Multidrug resistance in ATLL is likely mediated by P-gp over-expression.
  • P-gp may also play a significant role in multidrug resistance in a subset of PLL and CLL patients.
  • These findings highlight P-gp as a potential therapeutic target in specific drug-resistant lymphoproliferative disorders.