Related Experiment Video

Updated: Mar 8, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.9K

Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic

Jueqiong Wang1,2, Liu Lu1,2, Chung H Kok1,2

  • 1Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.

Haematologica
|February 4, 2017
PubMed

Insights

Peroxisome proliferator-activated receptor γ (PPARγ) activation reduces imatinib uptake in chronic myeloid leukemia (CML) cells by decreasing organic cation transporter-1 (OCT-1) activity. This suggests caution when combining PPARγ agonists with imatinib therapy.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Imatinib efficacy in chronic myeloid leukemia (CML) is linked to organic cation transporter-1 (OCT-1) activity.
  • Low OCT-1 activity correlates with poor molecular response to imatinib in CML patients.
  • Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor with known roles in metabolic and inflammatory processes.

Purpose of the Study:

  • To investigate the effect of PPARγ agonists and antagonists on OCT-1 activity in CML cells.
  • To determine the impact of PPARγ modulation on imatinib sensitivity and BCR-ABL kinase inhibition.
  • To explore the relationship between PPARγ transcriptional activity and OCT-1 activity in diagnostic CML patients.

Main Methods:

  • Assessed OCT-1 activity in diagnostic CML mononuclear cells and BCR-ABL1+ cell lines.
  • Utilized PPARγ agonists (e.g., GW1929, rosiglitazone, pioglitazone) and antagonists (e.g., GW9662, T0070907).
  • Confirmed results in PPARγ-transduced K562 cells and analyzed patient data (n=84) for correlations.

Main Results:

  • PPARγ agonists significantly decreased OCT-1 activity, while antagonists increased it in CML cells.
  • Modulation of OCT-1 activity by PPARγ ligands corresponded with changes in imatinib sensitivity.
  • A strong negative correlation was found between OCT-1 activity and PPARγ transcriptional activity in CML patients (P<0.0001).

Conclusions:

  • PPARγ activation negatively impacts imatinib intracellular uptake and BCR-ABL kinase inhibition in circulating CML mononuclear cells.
  • Inter-patient variability in PPARγ activation may explain heterogeneous OCT-1 activity at diagnosis.
  • Caution is advised when combining PPARγ agonists with imatinib, as effects on mononuclear cells may differ from stem cells and potentially counteract clinical benefits.

More Related Videos

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.7K
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

10.5K

Related Concept Videos

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...
9.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
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...
6.3K
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...
60