School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Ghudda, 151401, Bathinda, India.
Med Oncol. 2022 May 16;39(5):95. doi: 10.1007/s12032-022-01699-8.
Chronic myeloid leukemia (CML) is characterized by the possession of the Philadelphia chromosome, which contains the Bcr-Abl oncogene that codes for the oncoprotein BCR-ABL. Through glucose metabolism, glycolysis, and the translocation of the high-affinity glucose transporter to the cell surface, BCR-ABL modulates various signaling pathways in CML cells and maintains ATP turnover in tumor cells. Given the effective results of anti-tumor drugs in normalizing abnormal cellular metabolism, Imatinib (IM) has begun to be investigated and proven to be a highly potent tyrosine kinase inhibitor (TKI) in CML therapy. Initially, IM was tested for aberrant glucose metabolism, but all four metabolisms (glucose, lipid, amino acid, and nucleotide) are interrelated and enhance tumor growth under stress; eventually, the other three metabolisms were investigated. Subsequent effects of IM therapy showed a switch from glycolysis to the tricarboxylic acid cycle, upregulation of pentose phosphate pathway-associated oxidative pathways, and internal translocation of glucose transporters. In terms of lipid metabolism, IM had contradictory results: in one study, it served as a triglyceride and total cholesterol regulator, while in another study, it had no impact. The effect of IM on altered amino acid and nucleotide metabolisms was investigated using a multi-omics approach, which revealed a decrease in sulfur-containing amino acids, aromatic amino acids, and nucleotide biosynthesis. So, despite the mixed effect on cellular metabolism, IM has more positive effects, and therefore, the drug proved to be better than other TKIs. The present study is one approach to determine the transformative activities of IM against CML-associated metabolic changes, but further investigation is still needed to uncover more potentials of IM.
慢性髓性白血病 (CML) 的特征是拥有费城染色体，其中包含编码致癌蛋白 BCR-ABL 的 Bcr-Abl 癌基因。BCR-ABL 通过葡萄糖代谢、糖酵解以及将高亲和力葡萄糖转运蛋白易位到细胞表面，调节 CML 细胞中的各种信号通路，并维持肿瘤细胞中的 ATP 周转。鉴于抗肿瘤药物在使异常细胞代谢正常化方面的有效效果，伊马替尼 (IM) 已开始被研究并被证明是 CML 治疗中的一种高效酪氨酸激酶抑制剂 (TKI)。最初，IM 被测试用于异常葡萄糖代谢，但所有四种代谢（葡萄糖、脂质、氨基酸和核苷酸）都是相互关联的，并在应激下增强肿瘤生长；最终，研究了其他三种代谢。随后的 IM 治疗效果显示出从糖酵解向三羧酸循环的转变、戊糖磷酸途径相关氧化途径的上调以及葡萄糖转运蛋白的内部易位。就脂质代谢而言，IM 的结果存在矛盾：在一项研究中，它作为甘油三酯和总胆固醇调节剂，而在另一项研究中，它没有影响。使用多组学方法研究了 IM 对改变的氨基酸和核苷酸代谢的影响，结果表明含硫氨基酸、芳香族氨基酸和核苷酸生物合成减少。因此，尽管对细胞代谢的影响混合，但 IM 具有更多的积极作用，因此，该药物被证明优于其他 TKI。本研究是确定 IM 对 CML 相关代谢变化的转化活性的一种方法，但仍需要进一步研究以揭示 IM 的更多潜力。
