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Updated: Jul 24, 2026

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.
Abstract:
Acyclovir (ACV), a nucleoside analog, has been demonstrated previously to suppress selectively the proliferation of NIH3T3 fibroblastic cells transformed by either v-abl or bcr-abl gene transfection. From a viewpoint of clinical application of ACV, we investigated whether ACV inhibited the growth of leukemia cells expressing either p210 BCR-ABL or p185BCR-ABL. Acyclovir exerted an inhibitory effect on OM9;22 cells, p185BCR-ABL expressing cells, in a dose-dependent manner. Despite no down-modulation of a BCR-ABL tyrosine kinase activity or its expression was observed after treatment with ACV, cell cycle analysis demonstrated synchronization of OM9;22 cells at the G0/G1 phase. This suggests that, although ACV does not directly act on BCR-ABL tyrosine kinase, ACV may exert its inhibitory effect on some leukemia cell lines via alterations of the cell cycle. Although selective inhibition of Philadelphia chromosome-positive leukemia cell growth was not apparent, our data provides a therapeutic possibility for ACV in the treatment for leukemia.
Insights
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.
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