Effect of MI-3454 in combination with actinomycin D. (A) Viability of OCI-AML3 treated with DMSO, MI-3454 (25nM) or Act-D (5nM) as single agent or with the combination therapy of MI-3454 (25nM) and Act-D (5nM) (n=4). n indicates number of independent experiments. (B) Kaplan Maier plot of NSG mice injected with OCI-AML3 treated with DMSO, MI-3454, Act-D or the combination of MI-3454 and Act-D (n=8). n indicates number of independent NSG mice used per experimental arm. (C) Cell viability of BM cells originating from three primary NPM1c AML patients treated with DMSO, MI-3454, Act-D or the combination of MI-3454 and Act-D. (D) The difference in cell viability of SMC4 depleted OCI-AML3 cells versus scrambled control, measured 48h post-treatment with DSMO or Act-D. n indicates number of independent experiments. (E) No. of colonies in the colony forming assay of OCI-AML3 transduced with scrambled control and shRNA mediated SMC4 knockdown, treated with DMSO or Act-D (n=3). n indicates number of independent experiments. ∗P < 0.05; ∗∗P < 0.001; ∗∗∗P < 0.0001.