Effect of tipifarnib on antiproliferative effects of etoposide in clinical AML isolates. (A-C) Freshly isolated mononuclear cells from 3 newly diagnosed AML patients were plated in methylcellulose in diluent, 25 nM tipifarnib plus 50 to 200 nM etoposide, or 25 nM tipifarnib plus 50 to 200 nM etoposide as indicated. Bars represent relative colony counts observed after the indicated treatment. ○ represents relative colony counts predicted from the effects of the individual agents using the fractional product method.⁶¹  (D) Freshly isolated mononuclear cells from a newly diagnosed AML patient were plated in methylcellulose in the presence of etoposide alone (○), tipifarnib alone (inset), or 25 nM tipifarnib plus the indicated concentration of etoposide (●). (E) Combination index values⁵⁹  calculated from the data in panel D (●) and assays in samples from 3 other AML patients (○ and △) under conditions that are render the analysis equivalent to isobologram analysis.⁶⁰  Note that a combination index less than 1.0 indicates synergy.