Fig 2: AIC-47 disrupted the Warburg effect through dysregulation of the PKM1/PKM2 ratio. A, Expression profile of PKM isoforms in WT- and mutated-BCR-ABL-harboring cells at the steady state. PKM1 and PKM2 were detected by western blotting analysis under the same experimental conditions at the same time. B, Expression levels of PKM1,PKM2, and PKM mRNAs in TCCY cells at steady state. Expression level of mRNA was calculated by the ??C t method. Data are expressed as means ± SD of three different experiments. C, Expression of the Warburg effect-related proteins after treatment with DMSO (Control) or AIC-47 for 48 h. Expression levels of PTBP1, hnRNPA1, SRSF3, PKM1, PKM2 and PKM1/2 were examined by western blotting analysis. D, Ratio of PKM1/PKM2 was quantified by densitometry scanning. hnRNP, heterogeneous nuclear ribonucleoprotein; PKM, pyruvate kinase muscle; PTBP1, polypyrimidine tract-binding protein 1

Fig 3: Effects of silencing pyruvate kinase muscle (PKM) splicers on expression profile of PKM isoform. A,C,E, Expression profile of PKM isoform after transfection with siRNA for PTBP1 (A), hnRNPA1 (C) or SRSF3 (E) for 72 h. Expression levels of PTBP1, hnRNPA1, SRSF3, PKM1, PKM2 and PKM1/2 proteins were examined by western blotting analysis. B,D,F, Ratios of PKM1/PKM2 after silencing PTBP1 (B), hnRNPA1 (D), and SRSF3 (F) were quantified by densitometry scanning. hnRNP, heterogeneous nuclear ribonucleoprotein