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Abstract #0090

IDH-Mutant Gliomas Reprogram Glutamine Metabolism and Pyruvate Utilization: 1H NMR Spectroscopy based Consumption and Release Investigations

Vivek Tiwari1, Niraj K Gupta1, Rajni Chandak1, and Ashish Panigrahi1
1Indian Institute of Science Education and Research Berhampur, Berhampur, India

Synopsis

Keywords: Tumors (Pre-Treatment), Cancer

Motivation: IDH-mutant gliomas are associated with a favorable prognosis; however, the unique metabolic and cellular adaptations distinguishing IDH-mutant from IDH-wild-type gliomas are not yet comprehensively unraveled.

Goal(s): Investigate and quantify the metabolic pool and kinetics in IDH-mutant and wild-type gliomas using intracellular metabolite-profiling and Consumption and Release (CORE) dynamic measurements.

Approach: Metabolic pool and CORE dynamics were investigated using 1H-NMR (700 MHz), quantifying LN229 intracellular-metabolites together with CORE-measurements using metabolite estimations from Fresh-and-Spent media.

Results: IDH mutants showed higher Ki-67 and proliferation rate, significantly elevated intracellular-glutamine and glucose concentrations accompanied-with enhanced consumption of glutamine and glucose, and disrupted Pyruvate utilization in Anaplerotic and TCA-pathways.

Impact: 1H-NMR-based investigations and transcriptomic-profiling suggests that IDH-mutant gliomas undergo unique metabolic-adaptations, showing increased glutamine-glutamate dependency, disrupted pyruvate pathways, enhanced release of lactate. These findings indicate Glutamine-addiction in IDH-mutant-gliomas, pointing towards potential therapeutics targeted at glutamine metabolism for management of IDH-mutant-gliomas.

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