Extended Data Fig. 3: PABPC1 inhibition represses the translation of BCR-ABL1 and other leukemogenic transcripts in CML-BC.
a, Differentially expressed genes in K562 cells identified by RNA-seq. b, The top GO terms enriched in DEGs identified in (a). c, Relative BCR-ABL1 mRNA abundance per component to that in total RNA in MEG cells following PABPC1 inhibition (n = 3). d-e, Western blots showing BCR-ABL1 protein levels in MEG-01 cells following PABPC1 inhibition (d), or in BMCs of CML recipients in Fig. 2b (e) (n = 3 mice). f, Summary and definition of BCR-ABL1 downstream genes. g, Gene set enrichment analysis (GSEA) of BCR-ABL1 downstream genes using RNA-seq data (a). h, Differential expression of BCR-ABL1 downstream genes in leukemia cells derived from CML patients at different stages of disease, CML-CP (n = 42) and CML-BC (n = 28) patients from the GSE4170; CML patients (n = 9) before/after TKI treatment from the GSE33075; IM-resistant (n = 13) and remission (n = 83) CML patients from the GSE130404. i, Western blots showing BCR-ABL1 protein levels in K562 cells with PABPC1 inhibition rescued by BCR-ABL1 overexpression. j-k, Cell cycle distributions (j), early (Annexin V+-633-) and late (Annexin V+-633+) apoptosis (k) rates in K562 cells with PABPC1 inhibition rescued by BCR-ABL1 overexpression (n = 3). Data are shown as the mean ± SEM. P-values were determined by Student’s unpaired two-tailed t-test (a, h), and one-way ANOVA with Bonferroni correction (c, j, k), ns P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001.
