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- Title
Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia.
- Authors
Hubeek, I.; Peters, G. J.; Broekhuizen, A. J. F.; Sargent, J.; Gibson, B. E. S.; Creutzig, U.; Kaspers, G. J. L.
- Abstract
To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.
- Subjects
LEUKEMIA in children; ACUTE myeloid leukemia; DEOXYRIBONUCLEOTIDES; DRUG synergism; DRUG interactions; DRUG resistance; DNA repair
- Publication
British Journal of Haematology, 2005, Vol 131, Issue 2, p219
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2005.05760.x