ArticleBlood2007
Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.
- Not only a therapeutic target; mTOR in Hodgkin lymphoma and acute lymphoblastic leukemia.Frontiers in oncology · 2024Pooled it
- Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.International journal of molecular sciences · 2021Pooled it
- Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study.Bone marrow transplantation · 2009Trial
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- Decoding NOTCH1: From T-Cell Development Guardian to Driver of Pediatric T-Cell Lymphoblastic Lymphoma.International journal of molecular sciences · 2026Review
- Integrin-linked kinase (ILK) in hematologic malignancies: Bridging molecular mechanisms to therapeutic innovation.BioImpacts : BI · 2026Review
- Article
- Targeting Key Molecular Mechanisms in Triple-Negative Breast Cancer Therapies with Natural Compounds.Current pharmaceutical design · 2026Review
- G9a controls plasma cell differentiation through FOXO1 and ETS1 binding site regulatory networks.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling.Cell genomics · 2025Article
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Competitive signaling and cellular communications in myocardial infarction response.Molecular biology reports · 2025Review
- Notch signaling in cancer: metabolic reprogramming and therapeutic implications.Frontiers in immunology · 2025Review
- Single-cell resolution of intestinal regeneration in pythons without crypts illuminates conserved vertebrate regenerative mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.Journal of endocrinological investigation · 2024Article
- Defining the Regulatory Logic of Breast Cancer Using Single-Cell Epigenetic and Transcriptome Profiling.bioRxiv : the preprint server for biology · 2024Article
- Research progress on the role of PTEN deletion or mutation in the immune microenvironment of glioblastoma.Frontiers in oncology · 2024Review
- DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.Blood · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
92 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutive Notch activation is required for the proliferation of a subgroup of T-cell acute lymphoblastic leukemia (T-ALL). Downstream pathways that transmit pro-oncogenic signals are not well characterized. To identify these pathways, protein microarrays were used to profile the phosphorylation state of 108 epitopes on 82 distinct signaling proteins in a panel of 13 T-cell leukemia cell lines treated with a gamma-secretase inhibitor (GSI) to inhibit Notch signals. The microarray screen detected GSI-induced hypophosphorylation of multiple signaling proteins in the mTOR pathway. This effect was rescued by expression of the intracellular domain of Notch and mimicked by dominant negative MAML1, confirming Notch specificity. Withdrawal of Notch signals prevented stimulation of the mTOR pathway by mitogenic factors. These findings collectively suggest that the mTOR pathway is positively regulated by Notch in T-ALL cells. The effect of GSI on the mTOR pathway was independent of changes in phosphatidylinositol-3 kinase and Akt activity, but was rescued by expression of c-Myc, a direct transcriptional target of Notch, implicating c-Myc as an intermediary between Notch and mTOR. T-ALL cell growth was suppressed in a highly synergistic manner by simultaneous treatment with the mTOR inhibitor rapamycin and GSI, which represents a rational drug combination for treating this aggressive human malignancy.
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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.