ArticleOncotarget2013
Pharmacological targeting of the PI3K/mTOR pathway alters the release of angioregulatory mediators both from primary human acute myeloid leukemia cells and their neighboring stromal cells.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2026Review
- Evaluation of a Dual PI3K/mTOR Inhibitor PF-04691502 against Bladder Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences.Journal of clinical medicine · 2021Review
- Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- Article
- The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells.International journal of molecular sciences · 2020Review
- Article
- Biological Aspects of mTOR in Leukemia.International journal of molecular sciences · 2018Review
- The Angiogenic Chemokines Expression Profile of Myeloid Cell Lines Co-Cultured with Bone Marrow-Derived Mesenchymal Stem Cells.Cell journal · 2018Article
- Resistance to the Antiproliferative In Vitro Effect of PI3K-Akt-mTOR Inhibition in Primary Human Acute Myeloid Leukemia Cells Is Associated with Altered Cell Metabolism.International journal of molecular sciences · 2018Article
- SSeCKS/AKAP12 scaffolding functions suppress B16F10-induced peritoneal metastasis by attenuating CXCL9/10 secretion by resident fibroblasts.Oncotarget · 2017Article
- Review
- Targeting acute myeloid leukemia stem cell signaling by natural products.Molecular cancer · 2017Review
- The Complexity of Targeting PI3K-Akt-mTOR Signalling in Human Acute Myeloid Leukaemia: The Importance of Leukemic Cell Heterogeneity, Neighbouring Mesenchymal Stem Cells and Immunocompetent Cells.Molecules (Basel, Switzerland) · 2016Review
- Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway.Oncotarget · 2016Article
- Dual targeting of acute myeloid leukemia progenitors by catalytic mTOR inhibition and blockade of the p110α subunit of PI3 kinase.Oncotarget · 2015Article
- Downregulation of angiogenin inhibits the growth and induces apoptosis in human bladder cancer cells through regulating AKT/mTOR signaling pathway.Journal of molecular histology · 2015Article
- Inhibition of DNA methyltransferase as a novel therapeutic strategy to overcome acquired resistance to dual PI3K/mTOR inhibitors.Oncotarget · 2015Article
- Study on the function and mechanism of atorvastatin in regulating leukemic cell apoptosis by the PI3K/Akt pathway.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a heterogeneous and aggressive malignancy with poor overall survival. Constitutive as well as cytokine-initiated activation of PI3K/Akt/mTOR signaling is a common feature of AML patients, and inhibition of this pathway is considered as a possible therapeutic strategy in AML. Human AML cells and different stromal cell populations were cultured under highly standardized in vitro conditions. We investigated the effects of mTOR inhibitors (rapamycin and temsirolimus) and PI3K inhibitors (GDC-0941 and 3-methyladenin (3-MA)) on cell proliferation and the constitutive release of angioregulatory mediators by AML and stromal cells. Primary human AML cells were heterogeneous, though most patients showed high CXCL8 levels and detectable release of CXCL10, Ang-1, HGF and MMP-9. Hierarchical clustering analysis showed that disruption of PI3K/Akt/mTOR pathways decreased AML cell release of CXCL8-11 for a large subset of patients, whereas the effects on other mediators were divergent. Various stromal cells (endothelial cells, fibroblasts, cells with osteoblastic phenotype) also showed constitutive release of angioregulatory mediators, and inhibitors of both the PI3K and mTOR pathway had anti-proliferative effects on stromal cells and resulted in decreased release of these angioregulatory mediators. PI3K and mTOR inhibitors can decrease constitutive cytokine release both by AML and stromal cells, suggesting potential direct and indirect antileukemic effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.