Figure 2.
Combined IGF2BP3 knockdown and menin inhibition increases differentiation of MLL-Af4 leukemia. (A) Total colony numbers of MI-503–treated MLL-Af4 Lin– cells, depleted (I3KO) or nondepleted (NT) for IGF2BP3. MLL-Af4 Lin– NT and I3KO cells were treated with MI-503 0.5 μM for 4 days and seeded in methylcellulose colony formation assays at various initial seeding densities and cultured for 10 days. (B,C) Total colony number was reduced with both I3KO and MI-503 treatment at 0.5 μM (B) and 0.5 μM (C) in methylcellulose colony formation assays at initial seeding density of 2500. (D) Proportion of CFU-GM colonies are decreased with both I3KO and MI-503 (at 0.5 μM). (E-F) Proportion of CFU-G and -M colonies are increased with both I3KO and MI-503 (at 0.5 μM). (G-I) Lin–, c-kit+, and Lin–c-kit+ cells are decreased with both I3KO and MI-503. MLL-Af4 Lin– NT and I3KO cells were treated with MI-503 0.5 mM for 7 days and then analyzed by flow cytometric immunophenotyping; mean ± SD, n = 3; 1-way ANOVA with Bonferroni multiple comparison’s test (∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001). (J-M) Corresponding representative flow cytometry plots of MLL-Af4 Lin– NT and I3KO cells treated with MI-503 (or DMSO control), showing expression of c-kit and Lin markers. (N) Decreased CD34 expression by mean fluorescence intensity with I3KO; mean ± SD; n = 3; student t test, ∗P < .05. (O) Decreased CD16/32 expression by mean fluorescence intensity with MI-503 treatment; mean ± SD; n = 3; Student t test, ∗∗P < .01. (P-Q) Corresponding representative flow cytometry plots of MLL-Af4 Lin– NT and I3KO cells treated with MI-503 (or DMSO control), showing expression of CD16/32 and CD34. CFU-GM, granulocyte-macrophage colony-forming units; CFU-G, granulocyte colony-forming units; CFU-M, macrophage colony-forming units; MFI, mean fluorescence intensity; prop, proportion.

Combined IGF2BP3 knockdown and menin inhibition increases differentiation of MLL-Af4 leukemia. (A) Total colony numbers of MI-503–treated MLL-Af4 Lin– cells, depleted (I3KO) or nondepleted (NT) for IGF2BP3. MLL-Af4 Lin– NT and I3KO cells were treated with MI-503 0.5 μM for 4 days and seeded in methylcellulose colony formation assays at various initial seeding densities and cultured for 10 days. (B,C) Total colony number was reduced with both I3KO and MI-503 treatment at 0.5 μM (B) and 0.5 μM (C) in methylcellulose colony formation assays at initial seeding density of 2500. (D) Proportion of CFU-GM colonies are decreased with both I3KO and MI-503 (at 0.5 μM). (E-F) Proportion of CFU-G and -M colonies are increased with both I3KO and MI-503 (at 0.5 μM). (G-I) Lin–, c-kit+, and Lin–c-kit+ cells are decreased with both I3KO and MI-503. MLL-Af4 Lin– NT and I3KO cells were treated with MI-503 0.5 mM for 7 days and then analyzed by flow cytometric immunophenotyping; mean ± SD, n = 3; 1-way ANOVA with Bonferroni multiple comparison’s test (∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001). (J-M) Corresponding representative flow cytometry plots of MLL-Af4 Lin– NT and I3KO cells treated with MI-503 (or DMSO control), showing expression of c-kit and Lin markers. (N) Decreased CD34 expression by mean fluorescence intensity with I3KO; mean ± SD; n = 3; student t test, ∗P < .05. (O) Decreased CD16/32 expression by mean fluorescence intensity with MI-503 treatment; mean ± SD; n = 3; Student t test, ∗∗P < .01. (P-Q) Corresponding representative flow cytometry plots of MLL-Af4 Lin– NT and I3KO cells treated with MI-503 (or DMSO control), showing expression of CD16/32 and CD34. CFU-GM, granulocyte-macrophage colony-forming units; CFU-G, granulocyte colony-forming units; CFU-M, macrophage colony-forming units; MFI, mean fluorescence intensity; prop, proportion.

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