ReviewHaematologica2016
The relevance of PTEN-AKT in relation to NOTCH1-directed treatment strategies in T-cell acute lymphoblastic leukemia.
Review in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.EMBO molecular medicine · 2026Article
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.bioRxiv : the preprint server for biology · 2025Article
- Protective Effects of Velvet Antler Polypeptides on Cyclophosphamide-Induced Myelosuppression in Mouse and Bone Marrow Mesenchymal Stem Cells.Nutrients · 2025Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- The role of EphA7 in different tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- PTEN/PI3K/Akt pathway alters sensitivity of T-cell acute lymphoblastic leukemia to L-asparaginase.Scientific reports · 2022Article
- UCP2 silencing restrains leukemia cell proliferation through glutamine metabolic remodeling.Frontiers in immunology · 2022Article
- MET Inhibition Sensitizes Rhabdomyosarcoma Cells to NOTCH Signaling Suppression.Frontiers in oncology · 2022Article
- Noncoding RNAs in the Glycolysis of Ovarian Cancer.Frontiers in pharmacology · 2022Review
- The Genomic Landscape of a Restricted ALL Cohort from Patients Residing on the U.S./Mexico Border.International journal of environmental research and public health · 2021Article
- Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.Cell death & disease · 2021Article
- Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures.Nature communications · 2021Article
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia.Experimental hematology & oncology · 2020Review
- Biomarkers of immunotherapy in non-small cell lung cancer.Oncology letters · 2020Review
- Targeting lactate dehydrogenase A (LDHA) exerts antileukemic effects on T-cell acute lymphoblastic leukemia.Cancer communications (London, England) · 2020Article
- Article
- Combination Effect of Notch1 and PI3K/AKT/mTOR Signaling Pathways Inhibitors on T-ALL Cell Lines.International journal of hematology-oncology and stem cell research · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates phosphatidylinositol 3-kinase (PI3K)-AKT signaling and is often inactivated by mutations (including deletions) in a variety of cancer types, including T-cell acute lymphoblastic leukemia. Here we review mutation-associated mechanisms that inactivate PTEN together with other molecular mechanisms that activate AKT and contribute to T-cell leukemogenesis. In addition, we discuss how Pten mutations in mouse models affect the efficacy of gamma-secretase inhibitors to block NOTCH1 signaling through activation of AKT. Based on these models and on observations in primary diagnostic samples from patients with T-cell acute lymphoblastic leukemia, we speculate that PTEN-deficient cells employ an intrinsic homeostatic mechanism in which PI3K-AKT signaling is dampened over time. As a result of this reduced PI3K-AKT signaling, the level of AKT activation may be insufficient to compensate for NOTCH1 inhibition, resulting in responsiveness to gamma-secretase inhibitors. On the other hand, de novo acquired PTEN-inactivating events in NOTCH1-dependent leukemia could result in temporary, strong activation of PI3K-AKT signaling, increased glycolysis and glutaminolysis, and consequently gamma-secretase inhibitor resistance. Due to the central role of PTEN-AKT signaling and in the resistance to NOTCH1 inhibition, AKT inhibitors may be a promising addition to current treatment protocols for T-cell acute lymphoblastic leukemia.
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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.