Increased upregulation of genes involved in differentiation with IGF2BP3 knockdown and menin-MLL inhibition in MLL-Af4 leukemia, validated by qRT-PCR. (A-C) MI-503 treatment at 1.0 μM leads to downregulation of Igf2bp3 and known IGF2BP3 targets, Myc and Hoxa9, in MLL-Af4 Lin^– cells. (D-K) Upregulation of genes involved in differentiation with IGF2BP3 knockdown and MI-503 treatment. mRNA expression was measured by qRT-PCR in MLL-Af4 Lin^– cells depleted (I3KO) or nondepleted (NT) for IGF2BP3 and treated with MI-503 1.0 μM or DMSO control. Expression shown as fold change from NT DMSO (mean ± SD; n = 2; 1-way ANOVA with Bonferroni multiple comparisons test, ∗P < .05; ∗∗ P < .01; ∗∗∗P < .001; ∗∗∗∗ P < .0001).