Overcoming Imatinib Resistance in Chronic Myeloid Leukemia: A Metabolic Breakthrough Using GC–MS

Chronic myeloid leukemia (CML) is a disease that impacts thousands of people each year and developing effective treatments that can combat this disease is an urgent medical need. One of the biggest current challenges to developing treatments is the resistance to Imatinib (IM), which is a medication used to treat CML. By the use of a gas chromatography–mass spectrometry (GC–MS) metabolomics method, a research team from India explored a way to target the metabolic profile of IM-resistant CML cells.

Chronic myeloid leukemia (CML) in accelerated phase with thrombocytosis. Chronic myelogenous leukemia. | Image Credit: © Saiful52 - stock.adobe.com

Some research has already been done in this area, concluding that two microRNAs, hsa-miR-145-5p and hsa-miR-203a-5p, were capable of overcoming IM resistance (1). Furthermore, hsa-miR-203a-5p was found to influence glutathione metabolism in IM-resistant cells. The current study sought to delve deeper into whether these microRNAs could reverse IM resistance by modulating the overall metabolic characteristics of IM-resistant CML cells (1).

Using GC–MS, researchers conducted metabolic profiling of cell lysates obtained from IM-sensitive cells, IM-resistant cells, and IM-resistant cells transfected with hsa-miR-145-5p or hsa-miR-203a-5p. The analysis unveiled 75 major metabolites, with 32 in all samples (1). Pathway analysis conducted through MetaboAnalyst 5.0 revealed several enriched pathways, including those related to glucose metabolism, fatty acid biosynthesis, lipogenesis, and nucleotide metabolism (1).

Furthermore, 11 of these identified metabolites, such as l-glutamine, l-glutamic acid, l-lactic acid, and various fatty acids, exhibited higher concentrations in IM-resistant cells. Notably, the introduction of hsa-miR-145-5p or hsa-miR-203a-5p into IM-resistant cells led to a significant decrease in the levels of these metabolites (1). Particularly, hsa-miR-203a-5p demonstrated efficacy, evidenced by partial least-squares-discriminant analysis (PLS-DA), which revealed a metabolic profile similarity between IM-sensitive and IM-resistant cells transfected with hsa-miR-203a-5p (1).

These findings highlight the potential of GC–MS-based metabolic profiling to differentiate between drug-resistant and drug-sensitive CML cells. Moreover, this approach holds promise for routine monitoring of therapeutic responses in drug-resistant patients, paving the way for personalized treatment strategies (1).

The researchers’ efforts provided valuable insights into the mechanisms behind Imatinib resistance (1). By using GC–MS, the researchers also show a potential solution through microRNA-based metabolic modulation, which opens new avenues for more effective and personalized therapies for patients battling chronic myeloid leukemia (1).

Although further research and clinical trials are needed to validate these findings, the study represents a step forward in the ongoing fight against Imatinib resistance in CML. As the medical community continues to explore innovative approaches, the prospect of more successful and tailored treatments for CML patients is on the horizon.

This article was written with the help of artificial intelligence and has been edited to ensure accuracy and clarity. You can read more about our policy for using AI here.

Reference

(1) Singh, P.; Yadav, R.; Verma, M.; Chhabra, R. Analysis of the Inhibitory Effect of hsa-miR-145-5p and hsa-miR-203a-5p on Imatinib-Resistant K562 Cells by GC/MS Metabolomics Method. J. Am. Soc. Mass Spectrom. 2023, ASAP. DOI: 10.1021/jasms.3c00103