Extended Data Fig. 2: Comparison of T-ALL sensitivity to four ABL inhibitors.
a,b, PDX-derived leukemia cells were tested for sensitivity to each of the four inhibitors. A total of 11 cases were selected to represent dasatinib-sensitive vs resistant T-ALL and were xenografted in NSG mice to develop PDX. Mice were sacrificed once leukemia burden reached predefined endpoint, and human leukemia cells were harvested and subjected to drug sensitivity profiling ex vivo. Cells were incubated with increasing concentrations of each ABL inhibitor for 96 hours and cell viability was determined by flow cytometry as described in Methods. c, Dose-dependent cell death was determined for four ABL inhibitors in 8 T-ALL cell lines. HSB-2 (harbors TCR-LCK fusion), KOPT-K1 (harbors TCR-LMO2 fusion) and ALL-SIL (harbors ABL class fusion) were sensitive (LC50s are less than 0.05 nM) to both dasatinib and ponatinib but resistant to imatinib and nilotinib. For each leukemia case at each drug concentration, cells were tested in duplicates.
