Analysis of transcriptome differences in Karpas 299 cells after arsenic trioxide treatment by next-generation sequencing
In our previous study, we found that anaplastic large cell lymphoma (ALCL), especially anaplastic lymphoma kinase-positive (ALK+), is highly responsive to Arsenic Trioxide (ATO). We demonstrated that ATO can inhibit ALCL by reducing tyrosine phosphorylation of NPM-ALK in vitro and in vivo rather than by degrading NPM-ALK. To further explore the mechanism by which ATO inhibits the survival and growth of ALK+ ALCL cells, we treated Karpas 299 cells with 1.5 uM ATO for 24 hours then analyzed the differences in transcriptomes by next-generation sequencing. Gene Set Enrichment Analysis (GSEA) showed that both RESPONSE_TO_ARSENIC_TRIOXIDE and APOPTOSIS are positively correlated with ATO-treated cells. In contrast, we found a loss of the IL6_JAK_STAT3_SIGNALING and PI3K_AKT_MTOR_SIGNALING gene-expression signatures in ATO-treated cells. This indicated that the functions of the JAK/STAT pathway and the AKT/mTOR pathway are downregulated in these cells. Both of these pathways constitute important signaling pathways downstream of NPM-ALK. These results revealed that ATO has the potential to weaken NPM-ALK function specifically.