AI Article Synopsis
- Hypomethylating therapies like decitabine and azacitidine are being researched for treatment of conditions such as acute myeloid leukemia and myelodysplastic syndromes, as well as maintenance after stem cell transplants.
- These therapies work by reactivating genes silenced by methylation, allowing them to target cancer cells while minimizing damage to healthy stem cells at low doses.
- A new pharmacodynamic assay to measure levels of DNA methylase 1 (DNMT1) in circulating T cells may help refine the dosing and effectiveness of these therapies in clinical trials.
Article Abstract
Hypomethylating therapies using decitabine or azacitidine are actively investigated to treat acute myeloid leukemia, myelodysplastic syndromes, as maintenance therapy after allogenic stem cell transplant and hemoglobinopathies. The therapeutic mechanism is to de-repress genes that have been turned off through oncogenesis or development via methylation. The therapy can be non-cytotoxic at low dosage, sparing healthy stem cells and operating on committed precursors. Because the methods of determining maximum tolerated dose are not well suited to this paradigm, and because the mechanism of action, which is depletion of DNA methylase 1 (DNMT1), is complex and dependent on passing through a cell cycle, a pharmacodynamic assay that measures DNMT1 can inform clinical trials aimed at establishing and improving therapy. Herein, we provide an assay that measures DNMT1 relative levels in circulating T cells of peripheral blood.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/bs.mcb.2024.02.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!