Fig. 5: Timed inhibition of mTORC1 with chemotherapy improved AML burden.

a Experimental design of mTORC1 timed inhibition in combination with chemotherapy. MLL-AF9 cells (GPF+, CreERT::Rptorfl/fl) were transplanted 3 weeks before the start of chemotherapy (Doxā+āAra-C), which was started day 0 with (TAM) or without (Ctrl) Tamoxifen (TAM for 4 days started at day ā3, 0, or 5). b Kinetics of Raptor deletion efficiency days before (day 0) and after starting the 4 days of Tamoxifen (TAM) treatment (day 1, 3, 6, 8, 10, and 12) (nā=ā4). c AML burden with or without inducible Raptor deletion in combination with chemotherapy (nā=ā8). d Experimental design of retroviral transduction of hRAPTOR for rescue of Raptor deletion: The number of AML cells was evaluated at day 10 after initiation of chemotherapy (Doxā+āAraC). e AML burden with or without rescue: AML cell number per femur was evaluated. Empty vector and hRAPTOR were transfected (empty vector: nā=ā8, hRAPTOR nā=ā10). bāc, e Representative data from two independent experiments were shown. Meanā±āSEM was shown in bar pot (each dot represents each sample). Statistical analysis was performed by using two-way t-test (e) and paired t-test (b, c) (*pā<ā0.05, **pā<ā0.01, ***pā<ā0.001).