Expression profiling in exosomal miRNAs of CML patients with musculoskeletal pain associated with discontinuation of Imatinib

An approximately 60% of chronic myeloid leukemia (CML) patients who achieved a deep molecular response for more than 2 years maintained a major molecular response after discontinuation of imatinib. These findings indicate the possibility that a portion of CML patients treated with Tyrosine kinase inhibitors (TKIs) could discontinue TKI therapy, although long-term prognosis and/or adverse events after TKIs cessation remain unclear. Recent reports showed that transient musculoskeletal pain occurs in approximately 30% of CML patients after stopping imatinib. To ascertain the factors underlying musculoskeletal events after TKI cessation, we investigated exosomal miRNA in five CML patients who did not experience musculoskeletal events and five patients with musculoskeletal pain after stopping TKIs. Peripheral blood was obtained approximately 3 months after successful TKI cessation in CML patients. Exosomes were extracted by using Total Exosome Isolation Reagent, and the exosomal miRNA profiling was performed with a TaqMan Low-Density Array. The relative expression level of each gene was calculated by using the comparative thresholds cycle (Ct) method. Synthetic spike control (ath-miR-159) was used as an invariant control for the exosomal miRNA.