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. Author manuscript; available in PMC: 2021 Aug 27.
Published in final edited form as: Cell Metab. 2020 Aug 6;32(3):391–403.e6. doi: 10.1016/j.cmet.2020.07.009

Figure 2. Timed Inhibition of Glutamine Metabolism Overcomes Chemoresistance in AML.

Figure 2.

(A–C) Survival curves of MLL-AF9 AML-bearing mice treated with iCT and/or 6-diazo-5-oxo-L-norleucine (DON; 0.3 mg/kg i.p.) concomitantly (A, n = 5 mice per group) or sequentially (B and C). For sequential treatments, mice were either treated with 2 doses of DON at the moment of maximal response (B, n = 10 mice per group) or continuously with DON every other day following iCT (C, n = 5 mice per group). T, death due to drug toxicity; ^, moment of maximal response.

(D and E) Disease burden of MLL-AF9 AML-bearing mice treated sequentially with iCT and/or DON (regimen as in B), determined 1 day after the last dose of DON through bioluminescence imaging (D) or flow cytometry (E).

(F) Percentage of apoptotic cells in MLL-AF9 AML cells obtained from mice treated sequentially with iCT and/or DON (regimen as in B), determined 1 day after the last dose of DON.

(G) Survival curves of HoxA9/Meis1 AML-bearing mice treated sequentially with iCT and/or 2 doses of DON (0.3 mg/kg i.p.) specifically targeting the moment of maximal response (n = 5 mice per group). Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. See also Figure S2.