title: Aphidicolin decreases ex vivo resistance to cytosine arabinoside in childhood acute leukaemia.
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.
authors.affiliation: Haematology Research, Pembury Hospital, Kent, TN2 4QJ, UK. jean@mackaysargent.fsnet.co.uk
authors.forename: Jean M
authors.initials: JM
authors.lastname: Sargent
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Williamson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hubeek
authors.forename: Alena W
authors.initials: AW
authors.lastname: Elgie
authors.forename: Colin G
authors.initials: CG
authors.lastname: Taylor
authors.forename: Monique L
authors.initials: ML
authors.lastname: Den Boer
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Gertjan L
authors.initials: GL
authors.lastname: Kaspers
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D016590:Aphidicolin