Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate
Author Information
Author(s): Chou C. James, O'Hare Thomas, Lefebvre Sophie, Alvarez David, Tyner Jeffrey W., Eide Christopher A., Druker Brian J., Gottesfeld Joel M.
Primary Institution: The Scripps Research Institute
Hypothesis
1R-Chl is effective in blocking proliferation of cells harboring BCR-ABL mutations.
Conclusion
1R-Chl effectively inhibits the growth of BCR-ABL positive cells, including those resistant to imatinib.
Supporting Evidence
- 1R-Chl showed titratable inhibition of murine BM colony formation for unmutated Bcr-Abl and all studied mutations.
- 1R-Chl was effective against CML patient MNCs with an observed IC50 less than 125 nM.
- 1R-Chl displayed a high dose tolerance in murine models with no significant toxicity at therapeutic doses.
Takeaway
A new drug called 1R-Chl can stop cancer cells from growing, even the ones that don't respond to other treatments.
Methodology
The study involved testing 1R-Chl on BCR-ABL transduced murine bone marrow cells and primary cells from CML patients.
Limitations
Potential non-specific toxicity of 1R-Chl on normal human MNCs was observed.
Participant Demographics
The study included murine models and primary cells from CML patients and normal donors.
Digital Object Identifier (DOI)
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