RNA-Seq quantitative analysis of the regulatory effects of plasma exosomes from CML patients 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 plasma exosomes from TKI-resistant CML patients(R-Exo) promote drug resistance in CML compared to plasma exosomes from drug-sensitive CML patients (S-Exo). To shed light on the mechanism underlying 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 plasma exosomes from healthy controls (H-Exo), S-Exo, or R-Exo. We observed a significant upregulation in the expression of drug resistance-related genes and regulatory genes associated with fatty acid metabolism in K562 cells following R-Exo treatment. Overall design: RNA-seq profiling of K562 control cells, H-Exo-treated K562 cells, S-Exo-treated K562 cells, and the R-Exo-treated K562 cells.