Suppression of bcr-abl synthesis by siRNAs or tyrosine kinase activity by Glivec alters different oncogenes,

Related Experiment Video

Updated: Aug 23, 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

Zhivko Zhelev1, Rumiana Bakalova, Hideki Ohba

  • 1Single-Molecule Bioanalysis Laboratory, National Institute for Advanced Industrial Science and Technology, AIST-Shikoku, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.

FEBS Letters
|July 15, 2004
PubMed

Insights

Small interfering RNAs (siRNAs) effectively reduced bcr-abl mRNA and proliferation in chronic myelogenous leukemia cells. Both siRNA and Glivec treatments showed distinct gene expression changes without harming normal lymphocytes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Therapeutics

Background:

  • Chronic myelogenous leukemia (CML) is characterized by the BCR-ABL oncoprotein.
  • Targeting BCR-ABL is a key strategy for CML treatment.
  • Existing therapies like Glivec have limitations and resistance mechanisms.

Purpose of the Study:

  • To investigate the efficacy of small interfering RNAs (siRNAs) targeting BCR-ABL mRNA in CML.
  • To compare the molecular effects of siRNA treatment with Glivec in K-562 CML cells.
  • To analyze global gene expression changes induced by both therapeutic approaches.

Main Methods:

  • Design and transfection of short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) targeting BCR-ABL mRNA into K-562 cells.
  • Detection of ds/siRNA cellular penetration using fluorescent confocal microscopy.
  • Treatment of cells with a mix of three siRNA sequences or Glivec, followed by assessment of mRNA levels, protein tyrosine kinase activity, and cell proliferation.
  • Microarray analysis to compare gene expression profiles between siRNA- and Glivec-treated cells.

Main Results:

  • siRNA treatment significantly reduced BCR-ABL mRNA, p210 protein, tyrosine kinase activity, and cell proliferation.
  • Glivec treatment also reduced cell proliferation and tyrosine kinase activity, with minimal impact on p210.
  • Both treatments did not significantly affect normal lymphocyte viability.
  • Microarray analysis revealed distinct but overlapping gene expression changes, including downregulation of proto-oncogenes and upregulation of inflammatory and signaling pathway genes.

Conclusions:

  • siRNAs represent a viable therapeutic strategy for targeting BCR-ABL in CML, offering an alternative to Glivec.
  • Both siRNA and Glivec induce complex gene expression alterations, highlighting the multifaceted nature of BCR-ABL pathway modulation.
  • Further research into the specific gene targets and pathways affected by these treatments is warranted for optimizing CML therapy.

More Related Videos

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

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 specific...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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...
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...
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...