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They primarily harbor H3.3K27M mutations resulting in H3K27me3 reduction. Incorporated evaluation in H3.3K27M cells, tumors, and in vivo imaging in clients showed improved glycolysis, glutaminolysis, and tricarboxylic acid cycle metabolic rate with high alpha-ketoglutarate (α-KG) manufacturing. Glucose and/or glutamine-derived α-KG maintained low H3K27me3 in H3.3K27M cells, and inhibition of crucial enzymes in glycolysis or glutaminolysis increased H3K27
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