Identification of conserved IKAROS-regulated genes in BCR-ABL1⁺ B-ALL. (A) MA plot of average RNA-seq expression differences in B-ALL cells isolated from mice transplanted with primary Ikaros-kd (n = 7) versus control (n = 4) leukemias, highlighting genes with increased (red) or decreased (blue) expression at 5% FDR (Acceleration genes). (B) MA plot as in A for B-ALL cells isolated from mice bearing Ikaros-kd B-ALL (n = 7 independent primary leukemias), comparing 3 d Dox-treated mice to untreated mice. Genes with increased (red) or decreased (blue) expression at 5% FDR (Restoration genes) are highlighted. (C) Scatterplot of moderated t statistics of expressed genes in the Acceleration and Restoration experiments, highlighting genes that are differentially expressed (5% FDR) in both. Ikaros-activated genes are highlighted in orange, Ikaros-repressed genes in green, discordant genes in blue, and Ikaros/Ikzf1 and Ctnnd1 in red. (D and E) Venn diagrams of IKAROS-activated genes (D) and IKAROS-repressed genes (E) in the US and DCOG/COALL patient cohorts (both 1% FDR) intersected with Ikaros-activated and Ikaros-repressed genes identified in murine B-ALL (10% FDR). Conserved IKAROS-regulated genes are listed. (F) IKAROS ChIP-seq in human B-ALL cells showing significant binding peaks (gray bars) within and adjacent to the conserved IKAROS-repressed genes CTNND1, EMP1, and IFITM3.