ArticleLeukemia2005
PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways.
Article in Leukemia, 2005. 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 120 papers.
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Who cites it
120 citing papers in PubMed, 281 citations in OpenAlex.
- Oral MEK 1/2 Inhibitor Trametinib in Combination With AKT Inhibitor GSK2141795 in Patients With Acute Myeloid Leukemia With RAS Mutations: A Phase II Study.Clinical lymphoma, myeloma & leukemia · 2019Trial
- Preclinical and early clinical evaluation of the oral AKT inhibitor, MK-2206, for the treatment of acute myelogenous leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.Leukemia research · 2013Trial
- Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na.Leukemia research · 2012Trial
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- Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.Leukemia · 2026Article
- Unraveling the mechanism of mulberry leaf in alleviating hyperuricemia: key role of kaempferol by modulating AKT pathway and gut-kidney axis.Frontiers in microbiology · 2026Article
- Article
- Inhibition of α4β1 Integrin Activity by Small Tellurium Compounds Regulates PD-L1 Expression and Enhances Antitumor Effects.International journal of biological sciences · 2024Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine.Scientific reports · 2023Article
- Anti‑inflammatory effects of Nypa fruticans Wurmb via NF‑κB and MAPK signaling pathways in macrophages.Experimental and therapeutic medicine · 2022Article
- From Serendipity to Rational Identification of the 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-Pharmaceutics · 2022Article
- Copper Promotes Tumorigenesis by Activating the PDK1-AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- The relationship between NFKB, HER2, ER expression and anthracycline -based neoadjuvan chemotherapy response in local advanced stadium breast cancer: A cohort study in Eastern Indonesia.Annals of medicine and surgery (2012) · 2021Article
- Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.Journal of experimental & clinical cancer research : CR · 2020Article
- MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly.Journal of biomedical science · 2020Article
- A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia.BMC pharmacology & toxicology · 2020Article
60 more citing papers are in PubMed but not listed here.
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
The phosphoinositide 3-kinase (PI3-kinase) signalling pathway plays a key role in the regulation of cell survival and proliferation. We show that the PI3-kinase/Akt pathway is constitutively active in primary acute myeloid leukaemia (AML) cells and that blockade by the selective inhibitor LY294002 reduces survival of the total blast population (mean 52%). The ERK/MAPK module is also constitutively active and treatment with the MAPKK inhibitor U0126 reduces cell survival by 22%. In 10 of 18 samples, PI3-kinase contributes to MAPK activation as incubation with LY294002 leads to a marked reduction in its phosphorylation. PI3-kinase inhibition reduces survival of the CD34+38- AML progenitor subset by 44%, whereas MAPKK inhibition has little effect. Reporter assays in primary AML cells show that blocking PI3-kinase leads to a marked reduction of constitutive NF-kappaB activity and promotes p53-mediated transcription. This is associated with a synergistic interaction between LY294002 and Ara-C. An inducible activated form of Akt protects normal myeloid cells from Ara-C and etoposide-mediated apoptosis. These results show that blocking PI3-kinase has direct antileukaemic effects and potentiates the response to conventional cytotoxics via a number of targets including NF-kappaB, p53 and MAPK. Inhibitors of PI3-kinase and Akt may be useful in the treatment of AML.
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Registered trials
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.