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. 2007 Jun 19;97(2):253–259. doi: 10.1038/sj.bjc.6603853

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Copyright © 2007 Cancer Research UK

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Synergistic cytotoxicity produced by SJG-136 and fludarabine in primary CLL cells. (A) Dose–response curves were generated for CLL cells treated with SJG-136 and/or fludarabine. The cytotoxicity was quantified using an Annexin V/propidium iodide assay. (B) Median-effect plot. The cells were treated for 48 h with SJG-136 (1.0, 2.5, 5.0, 7.5, 10.0, 20.0 or 50 nM), fludarabine (0.1, 0.25, 0.5, 0.75, 1.0, 2.0 or 5.0 μM), or both at a fixed molar ratio of 1 : 100. The median-effect plot was constructed using Calcusyn software where Fa is the fraction affected and Fu the fraction unaffected. The fraction-affected CI plot was constructed by computer analysis of the data in (B) using the conservative isobologram (C). Combination index values of <1 occurred at a wide range of inhibition levels, indicating that synergy was produced by the combination. (D) Analysis of prognostic subsets revealed that there was diminished synergy in samples derived from patients with unmutated V_H genes, high CD38 expression and high ZAP-70 expression. However, this is likely to be the result of a preponderance of these samples demonstrating in vitro or in vivo fludarabine resistance.