Figure 1.

Asciminib and ponatinib synergize in producing growth inhibition in BCR-ABL1+ cell lines. The human CML cell lines KU812, K562, KCL22 and KCL22^T315I (A) and Ba/F3 cells expressing various BCR-ABL1-mutations (Ba/F3p210^T315I, Ba/F3p210^T315I/E255V, Ba/F3p210^T315I/F359V, Ba/F3p210^T315I/F311L, Ba/F3p210^T315I/G250E) or untransfected Ba/F3 cells supplemented with 10 ng/ml IL-3 (B) were kept in control medium or in the presence of asciminib (■-■), ponatinib (●-●), or a combination of both drugs at a fixed ratio (▲-▲) for 48 hours before ³H-thymidine-uptake was evaluated. Results are calculated as percent of control and represent the mean ± S.D. of triplicates. (C) The nature of drug interaction (additive versus synergistic) shown in (A) and (B) was determined for each experiment by calculating combination index (CI) values using Calcusyn software. A CI value of 1 indicates an additive effect, whereas CI values below 1 indicate synergistic drug effects. Examples are shown for K562 and KU812 as well as Ba/F3p210^T315I and Ba/F3p210^T315I/G250E cells as indicated.