Page 137 - Haematologica May 2020

MLL-rearranged AML requires MN1
Meningioma 1 regulates cell cycle, apoptosis and differentiation in MLL-AF9 cells
Next, we explored the impact of MN1 deletion on cell cycle, apoptosis and differentiation in MLL positive leukemic cell lines. Loss of MN1 inhibited cell cycle pro- gression resulting in more cells in G0/G1 phase and fewer cells in S phase of the cell cycle compared to MN1wt cells (Figure 2A and Online Supplementary Figure S4A). In addi-
tion, cell cycle progression was negatively associated with MN1 null cells by gene set enrichment analysis (GSEA) of gene expression profiling data (Online Supplementary Tables S4 and S5 and Online Supplementary Figures S4B and S5A- D). The proportion of Annexin V positive cells was signif- icantly increased and the gene sets for apoptosis and the p53 pathway were highly enriched in MLL-AF9/Mn1null cells (Figure 2B, Online Supplementary Table S4 and Online
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Figure 2. Meningioma 1 (MN1) regulates cell cycle, apoptosis and differentiation in MLL-AF9 cells. (A) Cell cycle analysis of MLL-AF9/Mn1wt and MLL-AF9/Mn1null cells [mean±standard error of mean (SEM), n=3]. (B) Proportion of apoptotic cells in MLL-AF9/Mn1wt and MLL-AF9/Mn1null cells (mean±SEM, n=3). (C) Relative gene expression of differentially expressed genes normalized to Abl1 in MLL-AF9/Mn1wt and MLL-AF9/Mn1null cells (mean±SEM, n=3). (D) Immunophenotype of in vitro cultured MLL-AF9/Mn1wt and MLL-AF9/Mn1null cells (mean±SEM, n=3). (E) Morphology of in vitro cultured MLL-AF9/Mn1wt and MLL-AF9/Mn1null cells (original magnification 1,000-fold). *P<0.05; **P<0.01; ns: not significant.
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