Related Experiment Video

Updated: May 27, 2026

HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
11:29

HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells

Published on: July 20, 2016

Translocation of nucleoside analogs across the plasma membrane in hematologic malignancies

Paula X Fernández-Calotti1, Dolors Colomer, Marçal Pastor-Anglada

  • 1Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona & CIBER EHD, Barcelona, Spain. pfernandezcalotti@ub.edu

Nucleosides, Nucleotides & Nucleic Acids
|December 3, 2011
PubMed

Insights

Nucleoside analogs treat blood cancers by inducing lymphoid cell apoptosis. Understanding nucleoside transporters (SLC28/SLC29) and efflux proteins (ABC) is key to improving drug delivery and effectiveness in chronic lymphocytic leukemia (CLL).

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Nucleoside analogs are vital for treating hematologic malignancies by inducing lymphoid cell apoptosis.
  • Cellular uptake and intracellular activation of these drugs depend on nucleoside transporters (SLC28/CNT and SLC29/ENT).
  • ATP-binding cassette (ABC) proteins mediate the efflux of activated nucleoside analogs.

Purpose of the Study:

  • To review nucleoside analogs used in hematologic malignancies, with a focus on chronic lymphocytic leukemia (CLL).
  • To discuss the role of nucleoside transporters in drug bioavailability and cellular sensitivity.
  • To explore the potential of modulating transporter activity to enhance therapeutic response in CLL.

Main Methods:

  • Literature review of nucleoside analogs and their mechanisms of action.
  • Analysis of the pharmacological profiles of nucleoside transporters (SLC28 and SLC29).
  • Discussion of transporter expression and activity in CLL cells.

Main Results:

  • Nucleoside analogs' efficacy is influenced by cellular uptake via SLC28/CNT and SLC29/ENT transporters.
  • Drug efflux by ABC proteins affects intracellular drug concentrations.
  • Nucleoside transporter expression and activity vary in CLL, impacting drug sensitivity.

Conclusions:

  • Targeting nucleoside transporters presents a promising strategy to optimize nucleoside analog therapy in CLL.
  • Modulating transporter activity can enhance intracellular drug availability and improve treatment outcomes.
  • Further research into transporter modulation is crucial for advancing CLL treatment.

More Related Videos

Radial Mobility and Cytotoxic Function of Retroviral Replicating Vector Transduced, Non-adherent Alloresponsive T Lymphocytes10:01

Radial Mobility and Cytotoxic Function of Retroviral Replicating Vector Transduced, Non-adherent Alloresponsive T Lymphocytes

Published on: February 11, 2015

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

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

Published on: June 17, 2022

Related Concept Videos

Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

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

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...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport

Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
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...