ERV reactivation drives PARPi sensitivity in murine Asxl1^-–/–Ezh2^–/– dKO cells. (A) The relative number of in vitro–deleted Asxl^–/–Ezh2^–/– dKO c-kit⁺ (n = 3) or WT c-kit⁺ cells (n = 3) are shown following the indicated in vitro treatment (P+D and P+L). (B) The bar chart shows the percentage of cells with ≥10 γH2AX foci upon the indicated treatment for Asxl^–/–Ezh2^–/– dKO c-kit⁺ or WT c-kit⁺ cells (top). Representative images of γH2AX foci (green) and their merge with DAPI (blue) are shown (bottom). (C) Comet assay was performed after the indicated treatments of Asxl^–/–Ezh2^–/– dKO c-kit⁺ cells and head length, tail length, and tail moment are shown in the violin plots (top). Example comet pictures are shown (bottom). (D) The relative number of Asxl1^–/–Ezh2^–/– dKO CLL cells (n = 5) are shown after the indicated treatment. (E) The bar chart shows the percentage of cells with ≥10 γH2AX foci after the indicated treatment of Asxl1^–/–Ezh2^–/– dKO CLL cells. (F) Comet assay was performed after the indicated treatment on Asxl^–/–Ezh2^–/– dKO CLL cells and head length, tail length, and tail moment are shown in the violin plots (top). Example pictures are shown (bottom). (G) Kaplan-Meier survival curves of mice transplanted with Asxl1^–/–Ezh2^–/– dKO CLL and treated in vivo as indicated are shown. Control, n = 11; PARPi, n = 13; RTi + PARPi, n = 12. Plots show mean ± SEM, ∗P < .05, ∗∗∗P < .001, ∗∗∗∗P < .001, unpaired t test. ns, not significant; P+D, PARPi + didanosine; P+L, PARPi + lamivudine.