ArticleLeukemia2007
Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts.
Article in Leukemia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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The trial behind it
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Who cites it
82 citing papers in PubMed, 198 citations in OpenAlex.
- Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.Leukemia research · 2013Trial
- GALNT5 drives colorectal cancer progression and chemoresistance via PI3K/Akt/ABCC1 axis.Journal of cancer research and clinical oncology · 2026Article
- Capivasertib Combines with Trastuzumab Deruxtecan to Enhance Antitumor Activity in HER2-Positive and HER2-Low Tumors.Molecular cancer therapeutics · 2026Article
- The RNA NCell death & disease · 2025Article
- NAT10 Knockdown Improves Cisplatin Sensitivity in Non-Small Cell Lung Cancer by Inhibiting the TRIM44/PI3K/AKT Pathway.Thoracic cancer · 2025Article
- Modulation of the Main Resistance-Associated ABC Transporter's Expression by Plant Flavonol Isorhamnetin.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The role and regulatory mechanism of lysosome associated protein transmembrane 4β in tumors.Frontiers in oncology · 2025Review
- Comparing Methods for Induction of Insulin Resistance in Mouse 3T3-L1 Cells.Current diabetes reviews · 2025Article
- The RNA NResearch square · 2024Article
- Inhibition of PI3K/Akt/mTOR Signaling Pathway Suppresses 5-Fluorouracil Resistance in Gastric Cancer.Molecular biotechnology · 2024Article
- Nanoparticle co-delivery of carboplatin and PF543 restores platinum sensitivity in ovarian cancer models through inhibiting platinum-induced pro-survival pathway activation.Nanoscale advances · 2024Article
- Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.Annals of hematology · 2024Review
- Histone acetylation: a key determinant of acquired cisplatin resistance in cancer.Clinical epigenetics · 2024Article
- USP10 suppresses ABCG2-induced malignant characteristics of doxorubicin-resistant thyroid cancer by inhibiting PI3K/AKT pathway.Journal of bioenergetics and biomembranes · 2023Article
- Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy.Cancer letters · 2023Review
- Down-Regulation of CYP3A4 by the KInternational journal of molecular sciences · 2023Article
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- Istradefylline induces A2A/P2X7 crosstalk expression inducing pro-inflammatory signal, and reduces AKT/mTOR signaling in melanoma-bearing mice.Medical oncology (Northwood, London, England) · 2023Article
- Review
- EGFR Transgene Stimulates Spontaneous Formation of MCF7 Breast Cancer Cells Spheroids with Partly Loss of HER3 Receptor.International journal of molecular sciences · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
A high incidence of relapses following induction chemotherapy is a major hindrance to patient survival in acute myelogenous leukemia (AML). There is strong evidence that activation of the phosphoinositide 3 kinase (PI3K)/Akt signaling network plays a significant role in rendering AML blasts drug resistant. An important mechanism underlying drug resistance is represented by overexpression of membrane drug transporters such as multidrug resistance-associated protein 1 (MRP1) or 170-kDa P-glycoprotein (P-gp). Here, we present evidence that MRP1, but not P-gp, expression is under the control of the PI3K/Akt axis in AML blasts. We observed a highly significant correlation between levels of phosphorylated Akt and MRP1 expression in AML cells. Furthermore, incubation of AML blasts with wortmannin, a PI3K pharmacological inhibitor, resulted in lower levels of phosphorylated Akt, downregulated MRP1 expression, and decreased Rhodamine 123 extrusion in an in vitro functional dye efflux assay. We also demonstrate that wortmannin-dependent PI3K/Akt inhibition upregulated p53 protein levels in most AML cases, and this correlated with diminished MRP1 expression and enhanced phosphorylation of murine double minute 2 (MDM2). Taken together, these data suggest that PI3K/Akt activation may lead to the development of chemoresistance in AML blasts through a mechanism involving a p53-dependent suppression of MRP1 expression.
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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.