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. 2021 Mar 24;218(5):e20200924. doi: 10.1084/jem.20200924

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© 2021 Stuani et al.

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Figure 4. — Treatment with an OxPHOS inhibitor enhances antileukemic effects of IDH^mi in vivo. (A) Number of colony-forming units following methylcellulose assays in two primary samples after a 17-d (AML6) and a 27-d incubation (AML5) with the indicated treatments. The numbers of colonies with ≥20 cells were counted manually under the microscope. See also Table S1 for patient information. (B) Experimental scheme detailing administration time of IACS-010759 and AG-120 by gavages in PDX models of AML. See also Table S1 for patient information. (C) AG-120 concentration in mice sera of PDXs 325 and 1065. (D) Total number of human viable AML cells expressing CD45 and CD33 in mono or duplet therapies compared with vehicle IDH1 R132 PDXs 325, 1065, 6312, and TUH110 in bone marrow and spleen. Fold change (FC) between the mean of each group and the mean of vehicle was calculated. (E) Intensity of CD15 staining (median) in bone marrow in mono and duplet therapies compared with vehicle-treated IDH1 R132 PDXs 325, 1065, 6312, and TUH110. (F) Aspartate and lactate levels normalized to control group in mice sera of IDH1 R132 PDXs 325 and 1065. For C–F, groups were compared with vehicle (no bracket) or other groups (corresponding brackets) with unpaired two-tailed t test with Welch’s correction. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Error bars indicate mean ± SEM. ctl, control.