Fig. 3: Pharmacologically targeting upregulated survival pathways in myelodysplastic syndrome stem cells reduces tumor burden and halts disease progression.
a, Numbers of live cultured LT-HSCs from CMP-pattern MDS patients with BP after treatment with 0.5 µM 5-aza (n = 6), 50 nM ABT-199 (ABT; n = 9) or the combination of the agents (n = 6) for 72 h. Lines represent means ± s.d. Statistical significance was calculated using one-way ANOVA and Tukey’s multiple-comparison test (****P < 0.0001). b, Human CD45 chimerism in total BM cells from MDS-L xenografts after one cycle of treatment with vehicle (n = 7), 5-aza (n = 5), ABT-199 (n = 6) or the combination of the agents (n = 5). Lines represent the means ± s.d. of one experiment. Statistical significance was calculated using one-way ANOVA and Tukey’s multiple-comparison test (****P < 0.0001, **P = 0.0049, *P = 0.038). c, Human CD45 chimerism in total BM white blood cells (WBCs) from xenografts of a CMP-pattern BP sample after treatment with vehicle (n = 8), 5-aza plus ABT-199 (n = 10) or with BMS-345541 (n = 7). Lines represent the means ± s.d. of two independent experiments. Statistical significance was calculated using one-way ANOVA and Tukey’s multiple-comparisons test (**P = 0.0056, *P = 0.02). d, Numbers of live cultured LMPPs isolated from samples of GMP-pattern MDS with BP (n = 6) after treatment with 5 µM BMS-345541 for 48 h in the presence of 2.5 ng ml−1 human-recombinant TNF. Lines represent means ± s.d. Statistical significance was calculated using a paired two-tailed Student t-test (***P = 0.0008). e, Human CD45 chimerism in total BM WBCs from xenografts of a GMP-pattern BP sample after treatment with vehicle (n = 11), BMS-345541 (n = 6) or with 5-aza plus ABT-199 (n = 4). Lines represent the means ± s.d. of three independent experiments. Statistical significance was calculated using one-way ANOVA and Dunnett’s multiple-comparisons test (****P < 0.001).
