Extended Data Fig. 7: MENIN and IKAROS display overlapping functions in regulation of gene expression.
a, Number of differentially expressed genes (greater than 2-fold change and adjusted p-value <0.05) from RNA-seq data for MOLM13 and MV4;11 cell lines treated with CC220 1 μM (n = 3), VTP-50469 50 nM (n = 3) and the combination (n = 3) for 3 days. b, Heatmap showing DESeq2 statistical z-score for all genes deregulated under treatment with VTP-50469 alone across all other treatment groups. c, Heatmap of DESeq2 statistical z-score for MENIN and IKAROS co-regulated gene expression. Showing genes with shared or additive regulation. Selected genes are indicated. d, Cell surface expression of FLT3 as measured by flow cytometry in the MOLM13 cell line. Cells were pre-treated for 2 days with CC220 or DMSO control and then VTP-50469 was added for 24 hours. e, CRISPR screen beta scores from MAGeCK MLE comparing sgRNA representation at day 0 compared to day 14 in the DMSO-treated control samples for the MOLM13 cell line. Negative beta scores for MYC, FLT3, RPA3 (common essential gene), RPS14, and BCL2 are indicated. f, Gene expression for IKZF1 as determined by RNA-seq in MOLM13 and MV4;11, indicating log-2-fold change value and adjusted p-value determined using DESeq2. g, Western blot analysis for IKAROS protein in the MOLM13 cell line following 5 days treatment with either VTP-50469 or iberdomide/CC220, followed by rescue treatment with bortezomib (BTZ) for 6 hours, using GAPDH as a loading control. Performed in the presence of the broad-spectrum caspase inhibitor, QV-D-OPH, to prevent cell death. h, Tornado plots depicting global IKAROS chromatin binding at TSSes, as determined by CUT&RUN in the MOLM13 cell line.
