Asciminib demonstrates varying efficacy against ABL1 and ABL2 fusion genes in vitro. In vitro targeting of ABL1 and ABL2 fusion genes with ponatinib (A,D), nilotinib (B,E), and asciminib (C,F). (A-F) LD50 concentrations from cell death assays targeting different ABL1 and ABL2 fusion genes identified in ALL. LD50 concentrations are from a minimum biological replicate of 3. (G-I) Intracellular flow cytometry of transduced Ba/F3 cells or patient blast cells and human CD45+ patient-derived xenograft (PDX) cells treated with asciminib (5 μM), imatinib (5 μM), nilotinib (1 μM), dasatinib (100 nM), or ponatinib (100 nM) for 2 to 6 hours and stained with antibodies for pSTAT5 and pCRKL. Untreated cells were used as controls. Percentage reductions in the presence of asciminib and TKIs (where cell number allowed) are specified. For the transduced cell lines, 3 biological replicates were performed. For patient and PDX samples, different symbols delineate individual patients. Columns represent mean ± standard deviation error bars with individual data points shown. Statistics were calculated by Student t test and significance is denoted with asterisks ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. DAS, dasatinib; IMAT, imatinib; MFI, mean fluorescence intensity.
