Fig. 4: Combined treatment with MEK and RUNX1 inhibitors reduced BCL-X_L and MCL-1 expression in CD11b⁺ myeloid cells.

A The bubble plot representing the top up-(left) and downregulated (top) hallmark gene sets in the comparison of S3 CD11b⁺ leukemic cells with the control (Mxcre or WT) cells. The gene ratio is represented on the y-axis, the bubble size corresponds to the gene count and the color map represents the adjusted p value. B The Ptpn11 mRNA expression level in the bone marrow LSK and spleen CD11b⁺ cells in the S3 leukemic (MxCre;Ptpn11^D61Y/+) and control (MxCre or WT) cells. The y-axis represents the logCPM (CPM- counts per million reads). C The gene set enrichment analysis of hallmark KRAS signaling up-regulated gene sets in the comparison of S3 spleen CD11b⁺ leukemic cells and LSK leukemic cells. The genes are ranked based on the fold change and the y-axis represents the running enrichment score (top) and the ranked list metric (bottom). The normalized enrichment score (NES), p value and adjusted p-value are shown in the table. Myeloid CD11b⁺ cells isolated from leukemic S2 mice or MxCre controls were treated with trametinib and/or Runx inhibitor for 24 h and then analyzed for expression of pro-survival proteins: D BCL-X_L and E MCL-1 and F % of specific apoptosis for myeloid cells (CD11b⁺ cells), monocytes (CD11b⁺Ly6C⁺) and neutrophils (CD11b⁺Ly6G⁺). All data are presented as Mean ±SEM (n = 1–10; ≥3 independent experiments).