Related Experiment Video
Updated: Jul 24, 2026
10:49
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Inhibitory effect of a nucleoside analog, acyclovir, on leukemia cells
J Nishimaki1, K Miyazawa, A Gotoh
1First Department of Internal Medicine, Tokyo Medical College, Japan.
Leukemia Research
|May 1, 1996
Summary
Acyclovir (ACV) inhibits leukemia cell growth by altering the cell cycle, not by directly targeting BCR-ABL tyrosine kinase. This suggests a potential therapeutic role for ACV in leukemia treatment.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Acyclovir (ACV), a nucleoside analog, previously showed selective suppression of NIH3T3 fibroblastic cells transformed by v-abl or bcr-abl.
- The clinical application of ACV for leukemia warrants investigation, particularly its effect on leukemia cells expressing BCR-ABL fusion proteins.
Purpose of the Study:
- To investigate the inhibitory effect of Acyclovir (ACV) on the growth of leukemia cells expressing p210 BCR-ABL or p185BCR-ABL.
- To explore the mechanism of ACV's action on leukemia cell proliferation.
Main Methods:
- Treatment of OM9;22 cells (p185BCR-ABL expressing) with Acyclovir (ACV).
- Assessment of BCR-ABL tyrosine kinase activity and expression levels post-ACV treatment.
- Cell cycle analysis using flow cytometry to determine cell cycle phase distribution.
Main Results:
- Acyclovir (ACV) demonstrated a dose-dependent inhibitory effect on OM9;22 leukemia cells.
- No significant down-modulation of BCR-ABL tyrosine kinase activity or expression was observed after ACV treatment.
- Cell cycle analysis revealed synchronization of OM9;22 cells at the G0/G1 phase, indicating cell cycle alteration.
Conclusions:
- Acyclovir (ACV) inhibits leukemia cell growth, potentially through cell cycle alterations rather than direct inhibition of BCR-ABL tyrosine kinase.
- While selective inhibition of Philadelphia chromosome-positive leukemia was not apparent, ACV presents a potential therapeutic strategy for leukemia treatment.
Related Concept Videos
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
01:28Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...