Fig. 1

NF-κB is responsible for gene expression changes in K562R cells. A Strategy for selection of genes contributing BCR-ABL-independent TKI resistance in CML. B Venn diagram showing upregulated and downregulated genes (fold-change ≥2) in K562R cells as examined by microarray and RNA-seq analyses. C Heat map analysis of expression levels of genes differentially expressed in K562R cells. D, E In silico analysis of transcription factors involved in regulating differentially expressed genes (in both the microarray and RNA-seq analyses) (D) or of three control group genes (each group contains 500 randomly selected genes) (E). The size and color represent the number of genes associated with the transcription factor. F Enrichment scores for transcription factors represent the degree of association with the differentially expressed genes compared to randomly selected genes, as detailed by the calculation listed in the Methods. G NF-κB and AP-1 luciferase reporter activities in K562S and K562R cells and in K562R cells treated for 24 h with 1 μM imatinib. H Quantitative reverse transcription PCR (qRT-PCR) analysis of the mRNA levels of 7 genes in K562S and K562R cells and in K562R cells treated with 1 μM imatinib for 24 h. IMA, imatinib. Data are representative of three (G, H) independent experiments (error bars, s.d. of duplicate (H) or triplicate (F, G) samples). Unpaired two-tailed t-test; *P < 0.05, **P < 0.01. NS, not significant; K562S, TKI-sensitive K562 cell line; K562R, BCR-ABL kinase domain mutation-free TKI-resistant K562 cell line