Targeting Herc1 modulates Ara-C response in vivo. (A) Schematic of the in vivo competition experiment. sgHerc1-mCherry cells and sgCtrl-BFP cells were combined in a 1:1 ratio before transplantation. A mix of 1 × 10⁶ cells was transplanted into sublethally irradiated C57BL6.J mice. MA and HM cells were analyzed at the indicated timepoints. (B) Representation of flow cytometry analysis of the peripheral blood (PB) and bone marrow (BM) before and after Ara-C treatment, as described in panel A, in a MA mouse who underwent transplantation. The in vivo competition experiment for MA (C) and HM cells (D). Every value represents the relative abundance of sgHerc1-mCherry AML cells in a mouse (MA, n = 11; HM, n = 10) at given timepoints. Significance was determined using paired t test. ∗∗∗∗P < .0001. MA and HM cells were normalized to pretreatment abundance in the PB. The results are from 2 independent experiments. (E) Assessment of Dck in Herc1–gene edited cells in vitro and 2 mice. BFP⁺ and mCherry⁺ cells were sorted before western blot analysis.