The following is a summary of “Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis,” published in the July 2024 issue of Hematology by Jiang et al.
Imatinib (IM) is the mainstay therapy for chronic-phase chronic myeloid leukemia (CML-CP) despite emerging resistance.
Researchers conducted a retrospective study to examine miR-629-5p expression in extracellular vesicles (EVs) derived from IM-sensitive (K562) and resistant (K562-Re) CML cell lines.
They assessed miR-629-5p levels in IM-sensitive and resistant CML cell lines. Subsequently, they isolated and verified EVs. The EVs from K562-Re cells were co-cultured with K562 cells to measure miR-629-5p expression. Target genes of miR-629-5p were identified and validated using luciferase assays. Transfection techniques were used to manipulate miR-629-5p expression. The levels of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway were examined post-IM treatment in CML cell lines. In K562-Re cells, phosphorylated protein levels in the PI3K/AKT/mTOR pathway were assessed following single miR-629-5p inhibitor transfection and co-transfection with miR-629-5p inhibitor and siSENP2.
The results showed that higher concentrations of EVs from K562-Re cells increased miR-629-5p expression levels. MiR-629-5p expression in CML cells varied with IM concentration, affecting cellular characteristics. The SENP2 was identified as a target gene of miR-629-5p. Additionally, miR-629-5p was found to regulate the SENP2/PI3K/AKT/mTOR pathway, influencing IM resistance in CML cells.
Investigators concluded that EVs derived from IM-resistant CML cells induced IM resistance in sensitive cells by modulating miR-629-5p expression and activating the SENP2/PI3K/AKT/mTOR pathway.
Source: tandfonline.com/doi/full/10.1080/16078454.2024.2379597
