a, Schematic of the HUSH complex in epigenetic silencing of retrotransposons. b, Depletion of HUSH proteins (PPHLN1 and TASOR) impaired MOLM-13 cell growth by the negative-selection competition assays. Results are mean ± SD (N = 3 independent experiments) and analyzed by a two-way ANOVA with Dunnett’s test. c, Depletion of other L1 regulators (MORC2, ATPIP7 and SETDB1) impaired MOLM-13 cell growth. Results are mean ± SD (N = 3 independent experiments) and analyzed by a two-way ANOVA with Dunnett’s test. d, Schematic of the xenotransplantation assay. e, Depletion of HUSH proteins (TASOR or PPHLN1) impaired MOLM-13 cell growth in NSG mice. Bioluminescence intensity is shown at 4 hours and 3 weeks post-transplantation. f, Quantification of bioluminescent imaging. Results are mean ± SD (N = 5 mice per group) and analyzed by a two-way ANOVA with Dunnett’s test. g, Representative image is shown for spleens of the xenografted NSG mice 3 weeks post-transplantation. h, Quantification of spleen weight 3 weeks post-transplantation. Results are mean ± SD (N = 3 mice per genotype) and analyzed by a one-way ANOVA with Dunnett’s test. i, Quantification of leukemia burden in PB, BM, spleen and liver of the xenografted NSG mice 3 weeks post-transplantation. Results are mean ± SD (N = 3 mice per group) and analyzed by a two-way ANOVA with Dunnett’s test. j, Kaplan-Meier survival curves of NSG mice xenografted with MOLM-13 cells transduced with control (sgNT) or sgRNAs against TASOR or PPHLN1. N = 5 mice per group. P values by a log-rank Mantel-Cox test.