Related Experiment Video

Updated: May 8, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

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

Published on: September 18, 2013

PKR negatively regulates leukemia progression in association with PP2A activation, Bcl-2 inhibition and increased

X Cheng1, R L Bennett, X Liu

  • 1Department of Medicine, Division of Hematology and Oncology and the University of Florida Shands Cancer Center, University of Florida, Gainesville, FL, USA.

Blood Cancer Journal
|September 10, 2013
PubMed

Insights

Reduced protein kinase R (PKR) activity hinders chemotherapy-induced apoptosis in leukemia by affecting protein phosphatase 2A (PP2A) and Bcl-2. Restoring PP2A activity with FTY720 re-sensitizes leukemia cells to chemotherapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Reduced protein kinase R (PKR) expression is linked to various cancers, including leukemia.
  • Loss of PKR function suggests a role in cancer progression and resistance to therapy.

Purpose of the Study:

  • To investigate the role of PKR in chemotherapy-induced apoptosis in leukemia.
  • To elucidate the downstream signaling pathways affected by PKR loss.
  • To evaluate the therapeutic potential of targeting the PKR pathway.

Main Methods:

  • In vitro and in vivo studies using leukemia cell lines and xenograft models.
  • Analysis of PKR, protein phosphatase 2A (PP2A), Bcl-2, and Bax protein levels and activity.
  • Assessment of apoptosis induction and mitochondrial membrane potential.
  • Treatment with PP2A activator FTY720.

Main Results:

  • Decreased PKR activity inhibited chemotherapy-induced apoptosis in leukemia cells.
  • PKR inhibition led to reduced PP2A activity, increased Bcl-2 phosphorylation, and impaired Bax insertion into mitochondria.
  • FTY720 treatment restored apoptosis and chemosensitivity in PKR-deficient cells.
  • Leukemic xenografts with reduced PKR showed increased tumor growth, chemoresistance, and reduced survival, which was reversed by FTY720.

Conclusions:

  • The PKR/PP2A signaling axis is crucial for stress-induced apoptosis in leukemia.
  • Loss of PKR promotes leukemia progression and chemoresistance.
  • Targeting PP2A activation may be a viable strategy to overcome chemoresistance in leukemia.
  • Reduced PKR expression could serve as a biomarker for predicting chemosensitivity.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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 daughter...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...