Alterations in cellular metabolisms after Imatinib therapy: a review

Kumar, Veerandra; Singh, Priyanka; Gupta, Sonu Kumar; Ali, Villayat; Jyotirmayee,; Verma, Malkhey

doi:10.1007/s12032-022-01699-8

Cited by 6 publications

(2 citation statements)

References 87 publications

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“…38,39 The metabolic transformations in the resistant tumor cells include aerobic glycolysis, enhanced fatty acid synthesis, de novo lipogenesis, and nucleotide biosynthesis to produce ATP. [30][31][32]40 In our study, too, we found that metabolites related to glucose metabolism, fatty acid synthesis, lipogenesis, and nucleotide biosynthesis were upregulated in IM-resistant K562 cells. The key metabolites of these pathways detected in our study include L-glutamine, Lglutamic acid, L-lactic acid, phosphoric acid, 9,12-octadecadienoic acid, 9-octadecenoic acid, myristic acid, palmitic acid, cholesterol, and β-alanine.…”

Section: ■ Discussionsupporting

confidence: 61%

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

Singh,

Yadav,

Verma

et al. 2023

J. Am. Soc. Mass Spectrom.

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Imatinib (IM) resistance is considered to be a significant challenge in the management of chronic myeloid leukemia (CML). Previous studies have reported that hsa-miR-145-5p and hsa-miR-203a-5p can overcome IM resistance and hsa-miR-203a-5p can alter glutathione metabolism in IM-resistant cells. The purpose of this study was to examine whether hsa-miR-145-5p or hsa-miR-203a-5p counters IM resistance by targeting the overall metabolic profile of IM-resistant K562 cells. The metablic profiling of cell lysates obtained from IM-sensitive, IM-resistant, and miR-transfected IM-resistant K562 cells was carried out using the GC-MS technique. Overall, 75 major metabolites were detected, of which 32 were present in all samples. The pathway analysis of MetaboAnalyst 5.0 revealed that the majorly enriched pathways included glucose metabolism, fatty acid biosynthesis, lipogenesis, and nucleotide metabolism. Eleven of identified metabolites, L-glutamine, L-glutamic acid, L-lactic acid, phosphoric acid, 9,12-octadecadienoic acid, 9-octadecenoic acid, myristic acid, palmitic acid, cholesterol, and β-alanine, appeared in enriched pathways. IM-resistant cells had comparatively higher concentrations of all of these metabolites. Notably, the introduction of hsa-miR-145-5p or hsa-miR-203a-5p into resistant cells resulted in a decrease in levels of these metabolites. The efficacy of miR-203a-5p was particularly remarkable in comparison with miR-145-5p, as evidenced by partial least-squares-discriminant analysis (PLS-DA), which showed a high level of similarity in metabolic profile between IMsensitive K562 cells and IM-resistant cells transfected with hsa-miR-203a-5p. The results indicate that GC-MS-based metabolic profiling has the potential to distinguish between drug-resistant and -sensitive cells. This approach can also be used to routinely monitor therapeutic response in drug-resistant patients, thus, enabling personalized therapy.

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Section: ■ Discussionsupporting

confidence: 61%

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

Singh,

Yadav,

Verma

et al. 2023

J. Am. Soc. Mass Spectrom.

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“…Several studies have focused on the metabolic effects induced by TKIs, reporting contrasting results between TKIs. In fact, imatinib has been shown to improve in vitro and in vivo glucose metabolism [41][42][43] through the internal translocation of glucose transporters (GLUT1, GLUT3, and GLUT6), by reducing glucose intake, switching from glycolysis to the tricarboxylic acid cycle, and increasing insulin secretion by limiting pancreatic b-cell apoptosis [44]. In addition, adiponectin, a hormone secreted by adipocytes with an important effect on insulin sensitivity regulation, has been found to increase in patients treated with imatinib.…”

Section: Metabolic Effectsmentioning

confidence: 99%

The Direct and Indirect Effects of Tyrosine Kinase Inhibitors on the Cardiovascular System in Chronic Myeloid Leukemia

Costa

Pittorru

Caocci

et al. 2023

Hemato

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Since their introduction, tyrosine kinase inhibitors (TKIs) have radically changed the treatment paradigm of Chronic Myeloid Leukemia (CML), leading to deep and lasting molecular responses and profoundly influencing survival. However, cancer-therapy-related Cardiovascular Toxicities (CTR-CVTs) associated with BCR::ABL1 TKIs are one of the main sources of concern: hypertension, arterial occlusive events, arrhythmias, dysmetabolic alteration, and glomerular filtration impairment are frequently reported in clinical trials and real-life experiences. Therefore, a close interaction between hematologists and cardiologists becomes crucial to implementing prevention protocols based on a comprehensive assessment of baseline cardiovascular risk, the management of any detectable and modifiable risk factors, and the elaboration of a monitoring plan for CTR-CVTs during treatment. Here, we provide the most comprehensive and recent evidence in the literature on the pathophysiological patterns underlying CTR-CVTs, providing useful evidence-based guidance on the prevention and management of CVD risk factors at baseline and during treatment with BCR::ABL1 TKIs.

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The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study

Fischer,

Luck,

Werle

et al. 2023

Chemistry and Physics of Lipids

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Alterations in cellular metabolisms after Imatinib therapy: a review

Cited by 6 publications

References 87 publications

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

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

The Direct and Indirect Effects of Tyrosine Kinase Inhibitors on the Cardiovascular System in Chronic Myeloid Leukemia

The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study

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