RNA-Seq quantitative analysis of the regulation of imatinib-resistant cell-derived exosomes on CML cell transcriptomes
Drug resistance frequently results in treatment failure for leukemia and leads to the progression of chronic myeloid leukemia (CML) into an accelerated or blast phase. Although new tyrosine kinase inhibitors (TKIs) and combined TKI therapies have been developed to address BCR-ABL1 mutation-induced drug resistance in CML patients, an increasing number of primitive CML cases exhibit reduced responsiveness or are unresponsive to TKIs. Herein, we discovered that drug-resistant CML cell-derived exosomes (R-Exo) promote resistance to imatinib (IM) in CML compared to drug-sensitive CML cell-derived exosomes (S-Exo). To shed light on the mechanism underlying R-Exo-induced CML drug resistance, we performed high throughput RNA-Seq analyses to reveal the differentially expressed genes in CML cells treated with or without R-Exo. We observed that there was a significant overlap in the expression of drug resistance-related genes that were altered in K562 upon R-Exo treatment. Of these, ATP-binding cassette subfamily B member 1 (ABCB1) exhibited the most obvious upregulation. Overall design: RNA-seq profiling of IM-sensitive and IM-resistant CML cells, R-Exo-treated K562 cells, and the S-Exo-treated K562 control group