Aphidicolin decreases ex vivo resistance to cytosine arabinoside in childhood acute leukaemia

Jean M Sargent, Christine J Williamson, Isabelle Hubeek, Alena W Elgie, Colin G Taylor, Monique L Den Boer, Godefridus J Peters, Gertjan L Kaspers

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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 languageEnglish
Pages (from-to)2027-31
Number of pages5
JournalOncology reports
Issue number6
Publication statusPublished - 10 Oct 2003
Externally publishedYes


  • 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


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