Fig. 5

The FLT3-TAZ signaling promotes TKI resistance via CD36-mediated fatty acid uptake. A Heatmap analysis of RNA-seq data from K562-mock, -FLT3, and TKI-resistant K562-FLT3-IR and -NR. The most strongly enhanced genes are labeled with red and the canonical YAP/TAZ target genes are labeled with blue. B Venn Diagram of TEAD4 ChIP-seq results comparing the overlap of direct TEAD4 target genes in HEK293A and K562-FLT3-IR cells. C ChIP-seq analysis showing TEAD4 and H3K27ac enrichment at the CD36 promoter region (highlighted) in HEK293A, K562-mock, and K562-FLT3-IR cells. D Immunoblotting analysis of CD36 protein levels in K562-FLT3-IR cells after treatment with TEAD inhibitor YBY-15 (0, 5, 10, 20 μM) for 16 h. E Measurements of CD36 transcript levels in K562-FLT3-IR cells treated with TEAD inhibitors flufenamic acid (Flu; 200 μM) or YBY-15 (15; 30 μM). F Metabolomic analysis of intracellular fatty acid derivatives in K562-FLT3-IR cells compared to K562-mock cells. G Lipid droplet analysis using BODIPY (green) staining in K562-mock and K562-FLT3-IR cells. DAPI (blue) was used as a nucleus marker. H Measurement of cell growth (left) and cell viability (right) in K562-FLT3 cells treated with imatinib (1 μM) treatment with or without CD36 inhibitor, SSO (200 μM). ****p < 0.0001. I Measurement of cell growth (left) and cell viability (right) of K562-FLT3-IR cells treated with normal or fatty acid-free medium with or without imatinib (1 μM). ****p < 0.0001; ns, not significant. E, H-I, All p-values were calculated using one-way ANOVA with Bonferroni corrections for multiple comparisons (E, I) and Student’s t-test (H). Error bars are means of triplicates ± SD. A p-value of less than 0.05 indicates a statistical difference