Enhanced Induction of Apoptosis in Chronic Myeloid Leukemia Cells Through Synergistic Effect of Telomerase Inhibitor Mst-312 and Imatinib Publisher Pubmed



Karami N^{1, 2} ; Navidinia AA^{2, 3} ; Ehsan M^{1, 4} ; Farsinejad A^{1, 5} ; Fatemi A⁶ Show Affiliations
Source: Molecular Biology Reports Published:2024

Abstract

Background: Chronic Myeloid Leukemia (CML), accounting for 15–20% of adult leukemia cases, is marked by the Philadelphia chromosome, resulting from the t(9;22)(q34;q11) translocation. This leads to uncontrolled cell proliferation and survival. Imatinib therapy lowers BCR-ABL levels, influencing telomere-associated proteins and increasing telomerase accessibility, indirectly boosting its activity. This study investigates the effects of MST-312 and imatinib, both individually and combined, on a CML cell line. Methods: The K562 cells were subjected to different doses of MST-312 and imatinib, including four combination concentrations. Cell viability and metabolic activity were measured using trypan blue and MTT assays at 24-, 36-, and 48-h post-treatment. Flow cytometry (AnnexinV/PI) assessed cell apoptosis after 36 h of treatment with MST-312 and imatinib, both individually and in combination. The expression levels of Bax, Bcl-2, hTERT, P21, P53, and c-Myc were determined via qRT-PCR. Results: Both MST-312 and imatinib independently reduced cell viability in a dose- and time-dependent manner. Their combination further decreased cell viability compared to monotherapy. Treatment of K562 cells with MST-312 and imatinib for 36 h increased Bax expression and the Bax/Bcl-2 ratio while decreasing Bcl-2 expression. Combined treatment significantly reduced hTERT ansd P21 gene expression compared to imatinib alone. Conclusions: The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance. © The Author(s), under exclusive licence to Springer Nature B.V. 2024.