FLT3 inhibitor AC220 impairs glutamine flux comparable to the glutaminase inhibitor CB-839 in AML cells. (A)
13C 15N-Glutamine tracing allows determining the fate of labeled carbon and nitrogen atoms derived from glutamine into various downstream metabolites. (B) Glutamine flux analysis of Molm13 AML cells treated with vehicle (dimethylsulfoxide), AC220 (2 nmol/L), or CB-839 (500 nmol/L). Cells were pretreated for 8 hours followed by 13C,15N-glutamine labeling for 3, 6, and 12 hours, as indicated, followed by ultra-high-performance liquid chromatography and mass spectrometry analysis. Levels of 13C- and 15N-containing isotopologues (based on signal intensity) are shown. (C) Diagram depicting mechanism of inhibition of glutamine metabolism by AC220 and CB-839.