The following is a summary of the “miR-495-3p sensitizes BCR-ABL1-expressing leukemic cells to tyrosine kinase inhibitors by targeting multidrug resistance 1 gene in T315I mutated cells,” published in the February 2023 issue of Experimental Hematology by Rittavee, et al.
Clonal haematological malignancy triggered by the BCR-ABL1 fusion oncoprotein defines chronic myeloid leukaemia (CML). Tyrosine kinase inhibitors (TKIs) have greatly improved patients’ chances of living a long time after their CML diagnosis. Nevertheless, amplification or mutations of the BCR-ABL1 oncogene and alterations in ATP-binding cassette (ABC) transporters account for about one-quarter of the patients who discontinue TKI treatment due to intolerance or resistance. There is mounting proof that the ATP-dependent efflux pump encoding gene MDR1 (multidrug resistance 1) is involved in miR-495-3p-mediated cancer chemoresistance.
Their study intended to deduce the molecular circuitry underpinning miR-495-probable 3p’s role in CML TKI chemo-sensitivity. They first noticed a decrease in miR-495-3p expression in in vitro cellular models expressing BCR-ABL1. Increased proliferation, decreased numbers of nondividing cells (G0/G1), and resistance to Imatinib were all seen in loss-of-function tests. Their results, on the other hand, demonstrated that overexpression of miR-495-3p inhibited leukemic cell proliferation, TKI resistance in Imatinib-resistant T315I-mutant cells, and drug efflux activity via modulation of MDR1.
Additional investigation into the involvement of miR-495-3p in CML patients revealed that expected miR-495-3p targets implicated in protein phosphorylation and linked with the worst prognosis were elevated in patients in blast crisis. Together, their findings highlight the importance of miR-495-3p downregulation in the malignant phenotype of CML and TKI resistance mechanisms, suggesting that miR-495-3p could serve as a biomarker and a therapeutic target in the fight to eradicate CML.