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Alterations in cellular metabolisms after Imatinib therapy: a review

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Abstract

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.

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Acknowledgements

The authors acknowledge the support received from the Banaras Hindu University, Varanasi in writing this manuscript. VK, PS, and VA are grateful to the CSIR, New Delhi, to award their fellowships.

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  1. Veerandra Kumar and Priyanka Singh have contributed equally to this work.

Authors and Affiliations

  1. School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Veerandra Kumar,  Jyotirmayee & Malkhey Verma

  2. Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Ghudda, 151401, Bathinda, India

    Priyanka Singh, Sonu Kumar Gupta & Villayat Ali

Authors
  1. Veerandra Kumar
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  2. Priyanka Singh
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  3. Sonu Kumar Gupta
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  4. Villayat Ali
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  5. Jyotirmayee
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  6. Malkhey Verma
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Contributions

MV conceived and designed this review. VK collected the literature and prepared the first draft of the manuscript. PS edited the manuscript and generated the figures. All authors have read and approved the final manuscript.

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Correspondence to Malkhey Verma.

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Kumar, V., Singh, P., Gupta, S.K. et al. Alterations in cellular metabolisms after Imatinib therapy: a review. Med Oncol 39, 95 (2022). https://doi.org/10.1007/s12032-022-01699-8

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