Abstract
In order to assess the effect of the DNA polymerase inhibitor aphidicolin on resistance to cytosine arabinoside, blast cells from 15 children with ALL and 9 with AML were exposed to a range of concentrations of ara-C +/- aphidicolin. Cell survival was measured using the MTT assay. Aphidicolin significantly increased sensitivity to ara-C in blast cells from both ALL (p=0.001) and AML (p<0.01). The median fold increase (sensitisation ratio) for ALL was 3.4 (range 1.2-13.6) compared to 12.4-fold (range 6.0-148) for AML blasts (p=0.005). There was a striking relationship between increasing ara-C resistance and increasing effect of aphidicolin in AML (p<0.001) but not ALL (p>0.05). These remarkable results suggest that aphidicolin should be considered for future clinical trials as a modulator of ara-C resistance, particularly in AML.
Original language | English |
---|---|
Pages (from-to) | 2027-31 |
Number of pages | 5 |
Journal | Oncology reports |
Volume | 10 |
Issue number | 6 |
DOIs | |
Publication status | Published - 10 Oct 2003 |
Externally published | Yes |
Keywords
- Aphidicolin/pharmacology
- Cell Survival
- Child
- Child, Preschool
- Clinical Trials as Topic
- Cytarabine/pharmacology
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- Drug Synergism
- Enzyme Inhibitors/pharmacology
- Female
- Humans
- Infant
- Leukemia, Myeloid, Acute/drug therapy
- Male
- Nucleic Acid Synthesis Inhibitors
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
- Time Factors