C-Myc inhibition intensified the anti-leukemic properties of Imatinib in chronic myeloid leukemia cells.

BACKGROUND

Due to its remarkable efficacy in producing hematologic, cytogenetic, and molecular remissions, the FDA approved Imatinib as the first-line treatment for newly diagnosed Chronic Myeloid Leukemia (CML) patients. However, in some patients, failure to completely eradicate leukemic cells and the escape of these cells from death will lead to the development of resistance to Imatinib, and many are concerned about the prospects of this Tyrosine Kinase Inhibitor (TKI). It has been documented that the compensatory overexpression of c-Myc is among the most critical mechanisms that promote drug efflux and resistance in CML stem cells.

METHODS

In order to examine the potential of c-Myc inhibition through the use of 10058-F4 to enhance the anti-leukemic properties of Imatinib, we conducted trypan blue and MTT assays. Additionally, we employed flow cytometric analysis and qRT-PCR to assess the effects of this combination on cell cycle progression and apoptosis.

RESULTS

The findings of our study indicate that the combination of 10058-F4 and Imatinib exhibited significantly stronger anti-survival and anti-proliferative effects on CML-derived-K562 cells in comparison to either agent administered alone. It is noteworthy that these results were also validated in the CML-derived NALM-1 cell line. Molecular analysis of this synergistic effect revealed that the inhibition of c-Myc augmented the efficacy of Imatinib by modulating the expression of genes related to cell cycle, apoptosis, autophagy, and proteasome.

CONCLUSIONS

Taken together, the findings of this investigation have demonstrated that the suppression of the c-Myc oncoprotein through the use of 10058-F4 has augmented the effectiveness of Imatinib, suggesting that this amalgamation could offer a fresh perspective on an adjunctive treatment for individuals with CML. Nevertheless, additional scrutiny, encompassing in-vivo examinations and clinical trials, is requisite.