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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)2027-2031
Number of pages5
JournalOncology Reports
Volume10
Issue number6
DOIs
Publication statusPublished - 2003

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