The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells
Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Malignant cell growth is characterized by disruption of normal intracellular signaling, caused by mutations or aberrant external signaling. Th...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/8/2907 |
| _version_ | 1797570039199563776 |
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| author | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Håkon Reikvam |
| author_facet | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Håkon Reikvam |
| author_sort | Ina Nepstad |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Malignant cell growth is characterized by disruption of normal intracellular signaling, caused by mutations or aberrant external signaling. The phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway (PI3K-Akt-mTOR pathway) is among one of the intracellular pathways aberrantly upregulated in cancers including AML. Activation of this pathway seems important in leukemogenesis, and given the central role of this pathway in metabolism, the bioenergetics of AML cells may depend on downstream signaling within this pathway. Furthermore, observations suggest that constitutive activation of the PI3K-Akt-mTOR pathway differs between patients, and that increased activity within this pathway is an adverse prognostic parameter in AML. Pharmacological targeting of the PI3K-Akt-mTOR pathway with specific inhibitors results in suppression of leukemic cell growth. However, AML patients seem to differ regarding their susceptibility to various small-molecule inhibitors, reflecting biological heterogeneity in the intracellular signaling status. These findings should be further investigated in both preclinical and clinical settings, along with the potential use of this pathway as a prognostic biomarker, both in patients receiving intensive curative AML treatment and in elderly/unfit receiving AML-stabilizing treatment. |
| first_indexed | 2024-03-10T20:19:25Z |
| format | Article |
| id | doaj.art-8d24d32feea140699db9853c7f75c266 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:19:25Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8d24d32feea140699db9853c7f75c2662023-11-19T22:18:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218290710.3390/ijms21082907The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) CellsIna Nepstad0Kimberley Joanne Hatfield1Ida Sofie Grønningsæter2Håkon Reikvam3Department of Clinical Science, University of Bergen, N-5021 Bergen, NorwayDepartment of Clinical Science, University of Bergen, N-5021 Bergen, NorwayDepartment of Clinical Science, University of Bergen, N-5021 Bergen, NorwayDepartment of Clinical Science, University of Bergen, N-5021 Bergen, NorwayAcute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Malignant cell growth is characterized by disruption of normal intracellular signaling, caused by mutations or aberrant external signaling. The phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway (PI3K-Akt-mTOR pathway) is among one of the intracellular pathways aberrantly upregulated in cancers including AML. Activation of this pathway seems important in leukemogenesis, and given the central role of this pathway in metabolism, the bioenergetics of AML cells may depend on downstream signaling within this pathway. Furthermore, observations suggest that constitutive activation of the PI3K-Akt-mTOR pathway differs between patients, and that increased activity within this pathway is an adverse prognostic parameter in AML. Pharmacological targeting of the PI3K-Akt-mTOR pathway with specific inhibitors results in suppression of leukemic cell growth. However, AML patients seem to differ regarding their susceptibility to various small-molecule inhibitors, reflecting biological heterogeneity in the intracellular signaling status. These findings should be further investigated in both preclinical and clinical settings, along with the potential use of this pathway as a prognostic biomarker, both in patients receiving intensive curative AML treatment and in elderly/unfit receiving AML-stabilizing treatment.https://www.mdpi.com/1422-0067/21/8/2907AktAMLchemotherapymetabolismmTORPI3K |
| spellingShingle | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Håkon Reikvam The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells International Journal of Molecular Sciences Akt AML chemotherapy metabolism mTOR PI3K |
| title | The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells |
| title_full | The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells |
| title_fullStr | The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells |
| title_full_unstemmed | The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells |
| title_short | The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells |
| title_sort | pi3k akt mtor signaling pathway in human acute myeloid leukemia aml cells |
| topic | Akt AML chemotherapy metabolism mTOR PI3K |
| url | https://www.mdpi.com/1422-0067/21/8/2907 |
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