ArticleBlood2009
Targeting the Notch1 and mTOR pathways in a mouse T-ALL model.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 137 citations in OpenAlex.
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Decoding NOTCH1: From T-Cell Development Guardian to Driver of Pediatric T-Cell Lymphoblastic Lymphoma.International journal of molecular sciences · 2026Review
- NSP6 of SARS-CoV-2 Dually Regulates Autophagic-Lysosomal Degradation.International journal of molecular sciences · 2025Article
- Ferroptosis: a new dawn in the treatment of acute lymphoblastic leukemia.Frontiers in oncology · 2025Review
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Endothelial cell-leukemia interactions remodel drug responses, uncovering T-ALL vulnerabilities.Blood · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- A Therapeutically Targetable NOTCH1-SIRT1-KAT7 Axis in T-cell Leukemia.Blood cancer discovery · 2023Article
- Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2021Review
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
- Article
- Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures.Nature communications · 2021Article
- Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review.Bosnian journal of basic medical sciences · 2021Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia.Experimental hematology & oncology · 2020Review
- Review
- Ponatinib Induces Vascular Toxicity through the Notch-1 Signaling Pathway.Journal of clinical medicine · 2020Article
- The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia.Cold Spring Harbor perspectives in medicine · 2020Review
- Current perspectives in T-ALL.HemaSphere · 2019Article
- Enhanced targeting of prostate cancer-initiating cells by salinomycin-encapsulated lipid-PLGA nanoparticles linked with CD44 antibodies.Oncology letters · 2019Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in NOTCH1 are frequently detected in patients with T-cell acute lymphoblastic leukemia (T-ALL) and in mouse T-ALL models. Treatment of mouse or human T-ALL cell lines in vitro with gamma-secretase inhibitors (GSIs) results in growth arrest and/or apoptosis. These studies suggest GSIs as potential therapeutic agents in the treatment of T-ALL. To determine whether GSIs have antileukemic activity in vivo, we treated near-end-stage Tal1/Ink4a/Arf+/- leukemic mice with vehicle or with a GSI developed by Merck (MRK-003). We found that GSI treatment significantly extended the survival of leukemic mice compared with vehicle-treated mice. Notch1 target gene expression was repressed and increased numbers of apoptotic cells were observed in the GSI-treated mice, demonstrating that Notch1 inhibition in vivo induces apoptosis. T-ALL cell lines also exhibit PI3K/mTOR pathway activation, indicating that rapamycin may also have therapeutic benefit. When GSIs are administered in combination with rapamycin, mTOR kinase activity is ablated and apoptosis induced. Moreover, GSI and rapamycin treatment inhibits human T-ALL growth and extends survival in a mouse xenograft model. This work supports the idea of targeting NOTCH1 in T-ALL and suggests that inhibition of the mTOR and NOTCH1 pathways may have added efficacy.
Indexed as
Identifiers
What OpenQuestion holds
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.