由于其在血液学、细胞遗传学和分子学缓解方面的显着功效，FDA 批准伊马替尼作为新诊断的慢性粒细胞白血病 (CML) 患者的一线治疗药物。然而，在一些患者中，未能彻底根除白血病细胞以及这些细胞免于死亡将导致对伊马替尼产生耐药性，许多人对这种酪氨酸激酶抑制剂（TKI）的前景感到担忧。据文献记载，c-Myc 的代偿性过表达是促进 CML 干细胞药物外流和耐药性的最关键机制之一。为了考察通过使用 10058-F4 增强 c-Myc 抑制的潜力，为了研究伊马替尼的抗白血病特性，我们进行了台盼蓝和 MTT 测定。此外，我们采用流式细胞术分析和qRT-PCR来评估该组合对细胞周期进程和凋亡的影响。我们的研究结果表明，10058-F4和伊马替尼的组合表现出明显更强的抗存活和抗增殖作用。与单独施用任一药物相比，对 CML 衍生的 K562 细胞的影响。值得注意的是，这些结果也在 CML 衍生的 NALM-1 细胞系中得到了验证。对这种协同效应的分子分析表明，c-Myc 的抑制通过调节与细胞周期、细胞凋亡、自噬和蛋白酶体相关的基因的表达来增强伊马替尼的功效。综上所述，本研究的结果表明，抑制通过使用 10058-F4 的 c-Myc 癌蛋白增强了伊马替尼的有效性，表明这种合并可以为 CML 患者的辅助治疗提供新的视角。然而，包括体内检查和临床试验在内的额外审查是必要的。© 2023。作者获得 Springer Nature B.V. 的独家许可。

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.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.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.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.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.