Figure 8. Target-specific inhibitors are effective in reducing B-NEG ALL primary cell proliferation.

A. Average values of ³H-thymidine incorporation of primary B-NEG ALL cells from 4 FLT3-mutated samples after 72 hours of treatment; crenolanib (0.1 μM) reduced the percentage of proliferating cells to 29.5±21.1%, quizartinib (0.1 μM) to 28.3±9.0% and ponatinib (0.1 μM) to 20.7±7.0%, on average. Compounds not targeting FLT3 (ruxolitinib and tofacitinib) proved ineffective. B. Average values of ³H-thymidine incorporation of primary B-NEG ALL cells from 4 samples carrying KRAS or NRAS mutations after 72 hours of treatment; BEZ235 (0.1 μM) reduced the percentage of proliferating cells to 21.3±9.0%, rapamycin (0.1 μM) to 37.8±21.1% and selumetinib to 62.4±16.9%, on average. Compounds not targeting PI3K/mTOR or MEK signaling (ruxolitinib and tofacitinib) proved ineffective. Each condition was run in triplicate. C. Average values of ³H-thymidine incorporation of primary B-NEG ALL cells from 4 FLT3-mutated and 4 FLT3-WT samples after 72 hours of treatment with crenolanib (0.1 μM). D. Average values of ³H-thymidine incorporation of primary B-NEG ALL cells from 4 RAS-mutated and 3 RAS-WT samples after 72 hours of treatment with rapamycin (0.1 μM).