Fig. 3. Topors is largely dispensable for normal hematopoiesis.

a Strategy for making a knockout allele for Topors by homologous recombination in embryonic stem cells. A large portion of exon 3 encoding amino acids 67 to 782 was replaced by a neo-cassette. b Representative PCR-based genotyping of mice obtained from breeding heterozygotes. Tail DNA was used as a template. Complete blood counts (c), proportions of myeloid cells (My; Mac-1⁺ and/or Gr-1+), B220+ B cells, and CD4⁺ or CD8+ T cells in PB (d), and proportions of BM HSPCs (e) in WT and Topors^−/− mice (2–4 months old) (n = 5 for each group, biological replicates). LSK Lin⁻Sca-1⁺c-Kit⁺; MP myeloid progenitor; CMP common myeloid progenitor; GMP granulocyte/macrophage progenitor; MEP megakaryocyte/erythrocyte progenitor. f Transplantation assays. Total BM cells (5 × 10⁶) from WT (red) and Topors^−/− (blue) mice were transplanted into lethally irradiated CD45.1 recipient mice. Complete blood counts and proportions of myeloid, B, and T cells in PB at 6 months post-transplantation are depicted (n = 6, biological replicates). g Growth of WT and Topors^−/− MLL-AF9-transformed cells in the presence and absence of DAC (n = 3 for each group, biological replicates). h Growth of WT and Topors^−/− c-Kit-positive cells in the presence and absence of DAC (n = 3 for each group, biological replicates). i In vivo treatment of MLL-AF9 leukemic cells with DAC. WT and Topors^−/− MLL-AF9 leukemic cells were transplanted into lethally irradiated recipient mice with support BM cells from CD45.1 mice. The recipient mice were treated with DAC from 4 to 6 weeks after transplantation. Chimerism of CD45.2 leukemic cells (left panels) and their absolute numbers (right panels) in PB at 4 and 6 weeks. The values of chimerism and absolute numbers at 6 weeks relative to those at 4 weeks (ratio) are also plotted, respectively (n = 9 for WT group, n = 10 for Topors^−/− group, biological replicates). *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.