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Published on: November 17, 2021
Targeting the reprogrammed metabolism in H3.3K27M pediatric high-grade gliomas
Eduardo S de Camargo Magalhães1, Eveline S J M de Bont2, Sophia W M Bruggeman3
1Department of Ageing Biology/ERIBA, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Glial Cell Biology Laboratory, Biomedical Sciences Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Recent studies in Diffuse Midline Gliomas (DMG) demonstrated a strong connection between epigenome dysregulation and metabolic rewiring. Here, we evaluated the value of targeting a glycolytic protein named Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase 3 (PFKFB3) in H3.3K27M DMG. We observed that the viability of H3.3K27M cells is dramatically reduced by PFK15, a potent inhibitor of PFKFB3. Furthermore, PFKFB3 inhibition induced apoptosis and G2/M arrest. Interestingly, CRISPR-Knockout of the K27M mutant allele has a synergistic effect on the observed phenotype. Altogether, we identified PFKFB3 as a new target for H3.3K27M DMG, making PFK15 a potential candidate for future animal studies and clinical trials.
