Metabolic Plasticity of Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Reprogramming of the Glycolytic Metabolism in AML
2.1. Increased Reliance on Glucose Consumption in AML
2.2. Cytosolic Carbohydrate Metabolism
2.3. Switch between Aerobic Glycolysis and OXPHOS: The Diverging Role in Hematopoietic Stem Cells and Leukemic Stem Cells
3. Mitochondrial Metabolism: TCA Cycle, OXPHOS and One-Carbon Metabolism in AML Biology and Treatment Resistance
3.1. TCA Cycle and OXPHOS in AML
3.2. Maintenance of Mitochondrial Mass and Respiratory Function
3.3. Metabolic Alterations in AML and Their Influence on the Epigenome
4. Amino Acid Metabolism in AML
4.1. Pleiotropic Functions of Glutamine
4.1.1. Glutamine as an Alternative Fuel for the TCA Cycle
4.1.2. Glutamine Deprivation Affects Redox Control
4.1.3. Glutamine Deprivation Affects mTORC1 Activity
4.2. Exploiting the Dependence of AML on Arginine
4.3. Branched-Chain Amino Acids
5. The Emerging Role of Lipid Metabolism in AML
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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No | Figures | Description | References |
---|---|---|---|
1 | 1, 2, 3 | Hexokinase is involved in resistance against FLT3-ITD inhibitors | [23] |
Hexokinase inhibition increases sensitivity against cytarabine | [30] | ||
Hexokinase is involved in resistance against daunorubicin | [38] | ||
2 | 1, 2, 3 | Glucose transporter (Glut1-Glut4) expression decrease chemotherapy sensitivity | [34,35] |
3 | 1, 2, 3 | Inhibition of the fructose transporter Glut5 enhances cytarabine cytotoxicity | [46] |
4 | 1, 3 | Amino acid consumption in oxidative phosphorylation may be associated with venetoclax sensitivity | [65,66] |
5 | 1, 3 | Mutated IDH1/2 are clinically validated targets for AML therapy | [77,78] |
6 | 1, 3, 4, 5 | Inhibition of glutaminase (GLS) synergizes with venetoclax and with AC220 | [93,97,98] |
7 | 1, 3, 7 | Fatty acid-oxidation may be related to venetoclax resistance | [66] |
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Kreitz, J.; Schönfeld, C.; Seibert, M.; Stolp, V.; Alshamleh, I.; Oellerich, T.; Steffen, B.; Schwalbe, H.; Schnütgen, F.; Kurrle, N.; et al. Metabolic Plasticity of Acute Myeloid Leukemia. Cells 2019, 8, 805. https://doi.org/10.3390/cells8080805
Kreitz J, Schönfeld C, Seibert M, Stolp V, Alshamleh I, Oellerich T, Steffen B, Schwalbe H, Schnütgen F, Kurrle N, et al. Metabolic Plasticity of Acute Myeloid Leukemia. Cells. 2019; 8(8):805. https://doi.org/10.3390/cells8080805
Chicago/Turabian StyleKreitz, Johanna, Christine Schönfeld, Marcel Seibert, Verena Stolp, Islam Alshamleh, Thomas Oellerich, Björn Steffen, Harald Schwalbe, Frank Schnütgen, Nina Kurrle, and et al. 2019. "Metabolic Plasticity of Acute Myeloid Leukemia" Cells 8, no. 8: 805. https://doi.org/10.3390/cells8080805