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

I. Hubeek, G. J. Peters, A. J.F. Broekhuizen, J. Sargent, B. E.S. Gibson, U. Creutzig, G. J.L. Kaspers

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Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)219-222
Aantal pagina's4
TijdschriftBritish Journal of Haematology
Volume131
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - okt. 2005
Extern gepubliceerdJa

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