Fig. 2: TOPORS-KO MDS/AML cells have an enhanced sensitivity to HMAs.

a Outline of competitive growth assays with HMAs and cytarabine. b Proportions of GFP-positive TOPORS-KO cells in culture, relative to those at day 1 in competitive growth assays using MOLM-13, MDS-L, SKK-1, and SKM-1 cells (n = 3 for each drug concentration, technical replicates, the experiments were repeated twice independently). Two different sgRNAs against TOPORS (sgTOPORS#1 and sgTOPORS#2) were tested. c Proportions of RFP-positive TOPORS-KO cells in culture, relative to those at day 1 in competitive growth assays using human MLL-AF9-transformed leukemic cells, in the presence and absence of 50 nM DAC (n = 3 for each group, biological replicates). d Western blot data of TOPORS in WT and TOPORS-KO MDS-L single clones. β-actin served as a loading control. The samples derive from the same experiment but different gels were processed in parallel. Growth of WT and TOPORS-KO MOLM-13 (e) and MDS-L (f) single clones in the presence and absence of DAC (n = 3 for each group, technical replicates, the experiments were repeated twice independently). Evaluation of the sensitivity of WT and TOPORS-KO MOLM-13 (g) and MDS-L cells (h) to DAC in xenograft models using NOG and NOG/IL-3/GM-CSF mice, respectively. Treatment timing and overall survival are depicted. Seven mice were analyzed for each group except for TOPORS-KO MDS-L vehicle (n = 6, biological replicates). Tumor burden in MDS-L recipients during DAC treatment (8–20 weeks post-transplantation) was measured by detecting Akaluc bioluminescence signals and relative tumor burden in DAC-treated groups compared with those in non-treated groups is depicted ((h), lower left panel). *p < 0.05; **p < 0.01; ***p < 0.001; n.s., not significant by unpaired two-tailed Student’s t-test. Data are presented as mean ± SD. Source data are provided as a Source Data file.