mTOR Regulation of Metabolism in Hematologic Malignancies
Abstract
:1. mTOR Structure and Function
2. Cancer Metabolism and Cell Signaling
3. mTOR and the Metabolism of Hematologic Malignancies
3.1. Acute Myeloid Leukemia
3.2. Chronic Myeloid Leukemia
3.3. Acute Lymphoblastic Leukemia
3.4. Chronic Lymphocytic Leukemia
3.5. Multiple Myeloma
3.6. Lymphomas
4. Summary and Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Target | Effect (Ref) |
---|---|---|
rapamycin | mTORC1 | Decreased Glucose uptake (59); |
Shift from Glycolysis to OXPHOS (61); | ||
Decreased glycolysis through PFKB3 downregulation (65) | ||
BKM-120 | PI3K | Decreased Glycolysis and OXPHOS |
2DG | Hexokinase | mTOR inactivation (62); |
mTOR activation (63) | ||
L-asparaginases | Asparagine and glutamine degradation | mTOR inactivation (70) |
Type | Compound | Target | Effect (Ref) |
---|---|---|---|
B-ALL | everolimus | mTORC1 | Decreased glycolysis and lactate generation (94) |
rapamycin | mTORC1 | Decrease of glycolysis and increase of OXPHOS, reversion of thiaminase effects (96) | |
T-ALL | 6-mercaptopurine | mTOR through AMPK activation | Decreased glucose and glutamine consumption (97) |
Type | Compound | Target | Effect (Ref) |
---|---|---|---|
PEL | LY294002 | PI3K | Decreased glycolysis and FAS (125) |
PF04691502 | PI3K/mTOR | Reduction of lactate production (126) | |
Akti 1/2 | Akt | Reduction of lactate production (126) | |
MCL | Everolimus | mTORC1 | Reduction of lactate production (127) |
AZD-2014 | mTORC1/2 | Downregulation of glycolytic enzymes (128) | |
DBLCL | 2DG | hexokinase | Inactivation of Akt/mTOR and decreased expression of Mcl-1 (129) |
rapamycin | mTORC1 | Reduction of OXPHOS and increase of glycolytic ATP in the oxidative DBLCL subset (130) |
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Mirabilii, S.; Ricciardi, M.R.; Tafuri, A. mTOR Regulation of Metabolism in Hematologic Malignancies. Cells 2020, 9, 404. https://doi.org/10.3390/cells9020404
Mirabilii S, Ricciardi MR, Tafuri A. mTOR Regulation of Metabolism in Hematologic Malignancies. Cells. 2020; 9(2):404. https://doi.org/10.3390/cells9020404
Chicago/Turabian StyleMirabilii, Simone, Maria Rosaria Ricciardi, and Agostino Tafuri. 2020. "mTOR Regulation of Metabolism in Hematologic Malignancies" Cells 9, no. 2: 404. https://doi.org/10.3390/cells9020404
APA StyleMirabilii, S., Ricciardi, M. R., & Tafuri, A. (2020). mTOR Regulation of Metabolism in Hematologic Malignancies. Cells, 9(2), 404. https://doi.org/10.3390/cells9020404