Related Experiment Video

Updated: May 18, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML

Paula Sabbo Bernardo1, Flaviana Ruade de Souza Reis, Raquel Ciuvalschi Maia

  • 1Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil.

Leukemia Research
|September 15, 2012
PubMed

Insights

Imatinib induces apoptosis in chronic myeloid leukemia (CML) cells by altering survivin localization. P-glycoprotein (Pgp) and survivin may be co-targeted for CML blast phase therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Chronic myeloid leukemia (CML) blast phase is an aggressive form of the disease.
  • Imatinib is a tyrosine kinase inhibitor used in CML treatment.
  • Survivin is a protein that inhibits apoptosis and is often dysregulated in cancer.

Purpose of the Study:

  • To investigate the effect of imatinib on apoptosis in P-glycoprotein (Pgp)-negative (K562) and Pgp-positive (Lucena) CML cell lines.
  • To determine the role of survivin localization in imatinib-induced apoptosis in CML.

Main Methods:

  • Cell viability assays (MTT)
  • Apoptosis detection (Annexin V/flow cytometry)
  • Protein localization analysis (immunocytochemistry, subcellular fractionation)
  • Protein expression analysis (Western blotting)

Main Results:

  • Imatinib significantly increased apoptosis in K562 cells, associated with nuclear survivin.
  • Imatinib showed a lower apoptotic effect in Lucena cells, with survivin localized in the cytoplasm.
  • P-glycoprotein (Pgp) expression correlated with cytoplasmic survivin and reduced imatinib sensitivity.

Conclusions:

  • Survivin localization (nuclear vs. cytoplasmic) influences imatinib-induced apoptosis in CML blast phase.
  • P-glycoprotein (Pgp) and survivin may share common regulatory pathways.
  • Targeting both Pgp and survivin could be a potential therapeutic strategy for CML blast phase.

Related Concept Videos

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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...