Fig. 1: Combined LSD1 inhibition and JAK-STAT signaling blockade synergize to produce anti-leukemic effects in ML-DS.

A Dose-response curves depicting cell viability of different ML-DS and non-DS-AMKL patient samples (expanded via xenotransplantation) after treatment with DMSO or 350 nM T-3775440 for 6 days, with the addition of serial dilutions of ruxolitinib from day 3 to day 6. All cell viability values were normalized to the corresponding all DMSO control. B Synergy blots displaying the color-coded Bliss synergy score, calculated after treatment of different ML-DS patient samples (expanded via xenotransplantation) with T-3775440 and ruxolitinib for 6 days. Interpretation of synergy scores: >10 drug synergy; −10 to 10 additive effects; <−10 drug antagonism. C Treatment schedule of humanized recipient mice transplanted with the ML-DS #1 patient sample. D Spleen weights in milligrams of mice engrafted with the ML-DS #1 patient sample, after treatment with placebo, T-3775440, ruxolitinib, or the combination of both drugs for 7 days. E Bone marrow infiltration in mice engrafted with the ML-DS #1 patient sample, after treatment with placebo, T-3775440, ruxolitinib, or the combination of both drugs for 7 days. Infiltration was defined as percentage of human myeloid blasts and was measured by flow cytometry. Human myeloid blasts were defined as CD45⁺ and CD33⁺. ns p > 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; p values are derived from two-tailed Student’s t tests comparing two groups. ML-DS myeloid leukemia associated with Down syndrome, non-DS-AMKL acute megakaryoblastic leukemia not associated with Down syndrome, DMSO dimethyl sulfoxide.