Transcriptional intrinsic and extrinsic persistence mechanisms to crizotinib in ALK+ ALCL cells. (A) PCA of SUPM2 and L82 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (B) Venn diagram of the upregulated genes in SUPM2 cells cocultured with MS-5 vs alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (C) Venn diagram of the upregulated genes in L82 cells cocultured with MS-5 vs alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (D) Venn diagram of the upregulated genes in SUPM2 cells treated with crizotinib (20-50-100 nM) for 72 hours vs NT. (E) Venn diagram of the upregulated genes in L82 cells treated with crizotinib (20-50-100 nM) for 72 hours vs NT. (F) Heat map revealing the expression of selected genes in SUPM2 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (G) Heat map revealing the expression of selected genes in L82 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (H) Dot plot reporting the upregulation and downregulation of selected pathways in SUPM2 cells treated with crizotinib (50-100 nM) for 72 hours vs NT, in the presence or absence of MS-5. The color of the dots indicates the P value adjusted, whereas their size relates to the number of enriched gene sets among the analyzed collections. (I) Dot plot reporting the upregulation and downregulation of selected pathways in L82 cells cocultured with MS-5 vs alone and treated with crizotinib (50-100 nM) for 72 hours. The color of the dots indicates the P value adjusted, whereas their size relates to the number of enriched gene sets among the analyzed collections.
Figure 3.

Transcriptional intrinsic and extrinsic persistence mechanisms to crizotinib in ALK+ ALCL cells. (A) PCA of SUPM2 and L82 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (B) Venn diagram of the upregulated genes in SUPM2 cells cocultured with MS-5 vs alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (C) Venn diagram of the upregulated genes in L82 cells cocultured with MS-5 vs alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (D) Venn diagram of the upregulated genes in SUPM2 cells treated with crizotinib (20-50-100 nM) for 72 hours vs NT. (E) Venn diagram of the upregulated genes in L82 cells treated with crizotinib (20-50-100 nM) for 72 hours vs NT. (F) Heat map revealing the expression of selected genes in SUPM2 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (G) Heat map revealing the expression of selected genes in L82 cells cocultured with MS-5 or cultured alone and treated with crizotinib (nt-20-50-100 nM) for 72 hours. (H) Dot plot reporting the upregulation and downregulation of selected pathways in SUPM2 cells treated with crizotinib (50-100 nM) for 72 hours vs NT, in the presence or absence of MS-5. The color of the dots indicates the P value adjusted, whereas their size relates to the number of enriched gene sets among the analyzed collections. (I) Dot plot reporting the upregulation and downregulation of selected pathways in L82 cells cocultured with MS-5 vs alone and treated with crizotinib (50-100 nM) for 72 hours. The color of the dots indicates the P value adjusted, whereas their size relates to the number of enriched gene sets among the analyzed collections.

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