Apoptotic synergism between STI571 and the farnesyl transferase inhibitor SCH66336 on an imatinib-sensitive cell line.

I have read the very interesting and informative article of Hoover et al,1 which may open new avenues in treating imatinib-refractory and imatinib-sensitive chronic myeloid leukemia (CML). However, when testing the synergic potential of STI farnesyl transferase inhibitor (FTI) combination on the STI571-sensitive Baf BCR-ABL-s cell line, a deficient statistical proof is shown. In their Figure 2A, an analysis of variance result is provided with a P .019 at 24 hours of treatment. The comparison, although, was made between 4 experimental conditions (dimethyl sulfoxide [DMSO], STI571, FTI, and combination), and no post hoc tests (as the Bonferroni one) are reported to compare the most relevant treatments, STI571, and the combination with FTI. So, with the kinetic cell-death data the paper shows, no additive or synergistic interaction can be stated. Both assays, measuring the annexin V and caspase 3 levels,1(Fig 2F-G) also suggest an increased apoptosis with the combination, but again a lack of adequate statistic analysis hampers any estimation of increased therapeutic effect. A clear-cut evidence of a faster BCR-ABL , STI571-sensitive cell apoptosis is a desirable goal, if the combined therapy is to be tested in vivo to treat imatinib-sensitive CML.