Patients with leukemia harboring NTRK mutations show altered sensitivity to small-molecule inhibitors of various signaling pathways. (A) Inhibitor profile for patient 12-00171, with the IC₅₀ response to each inhibitor shown on a log₁₀ scale relative to the median IC₅₀ of all primary samples tested to date. Dotted line indicates 20% of the median IC₅₀, which has historically been a marker for patient samples remarkably sensitive to a screened inhibitor.^34,44  Inhibitors targeting the indicated families are colored, and then emphasized with the breakout panel on the right (drugs targeting other families are removed from the chart). (B) Inhibitor profile for patient 12-00337, all drugs with IC₅₀ responses less than the median IC₅₀ are shown in the breakout panel on the right and labeled. (C) siRNA screen targeting tyrosine kinases in patient 10-00828. Targets are compared against nontargeting control, with unadjusted P values derived from a Student 2-tailed t test (n = 3 for each target) shown on the y-axis (negative log₁₀ scale), and effect size shown as difference in median viability on the x-axis. NTRK2 and NTRK3 knockdown resulted in reduced cell viability.