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The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies

1
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2
Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy
3
Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Cristina Papayannidis
Int. J. Mol. Sci. 2021, 22(6), 3135; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063135
Received: 19 February 2021 / Revised: 10 March 2021 / Accepted: 16 March 2021 / Published: 19 March 2021
(This article belongs to the Special Issue Metabolism and Leukemia: From Biology to Therapies)
The study of metabolic deregulation in myeloid malignancies has led to the investigation of metabolic-targeted therapies considering that cells undergoing leukemic transformation have excessive energy demands for growth and proliferation. However, the most difficult challenge in agents targeting metabolism is to determine a window of therapeutic opportunities between normal and neoplastic cells, considering that all or most of the metabolic pathways important for cancer ontogeny may also regulate physiological cell functions. Targeted therapies have used the properties of leukemic cells to produce altered metabolic products when mutated. This is the case of IDH1/2 mutations generating the abnormal conversion of α-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). Additional observations derive from the high sensitivity of leukemic cells to oxidative phosphorylation and its amelioration using BCL-2 inhibitors (Venetoclax) or by disrupting the mitochondrial respiration. More recently, nicotinamide metabolism has been described to mediate resistance to Venetoclax in patients with acute myeloid leukemia. Herein, we will provide an overview of the latest research on the link between metabolic pathways interactome and leukemogenesis with a comprehensive analysis of the metabolic consequences of driver genetic lesions and exemplificative druggable pathways. View Full-Text
Keywords: myeloid malignancies; TET2 mutations; IDH1/2 mutations; venetoclax; nicotinamide myeloid malignancies; TET2 mutations; IDH1/2 mutations; venetoclax; nicotinamide
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MDPI and ACS Style

Gurnari, C.; Pagliuca, S.; Visconte, V. The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies. Int. J. Mol. Sci. 2021, 22, 3135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063135

AMA Style

Gurnari C, Pagliuca S, Visconte V. The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies. International Journal of Molecular Sciences. 2021; 22(6):3135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063135

Chicago/Turabian Style

Gurnari, Carmelo, Simona Pagliuca, and Valeria Visconte. 2021. "The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies" International Journal of Molecular Sciences 22, no. 6: 3135. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063135

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