ArticleNature medicine2012
NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-θ and reactive oxygen species.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- The Novel Organic Arsenical PZ2 Exhibits Potent Anti-T-ALL Activity via ROS-Dependent Apoptosis andCancers · 2026Article
- Notch-1 suppressed vascular dementia via modulating AMPK/mTOR/TFEB/YAP signaling induced ferroptosis.European journal of medical research · 2026Article
- The Dual Role of RUNX1 in Inflammation-Driven Age-Related Diseases: From Molecular Mechanisms to Clinical Translation.Biomedicines · 2025Review
- The circadian clock circuitry modulates leukemia initiating cell activity in T-cell acute lymphoblastic leukemia.Journal of experimental & clinical cancer research : CR · 2023Article
- RUNX1 colludes with NOTCH1 to reprogram chromatin in T cell acute lymphoblastic leukemia.iScience · 2023Article
- Transcriptomic Context ofBiomedicines · 2023Article
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
- Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Review
- PD-1 signalling defines and protects leukaemic stem cells from T cell receptor-induced cell death in T cell acute lymphoblastic leukaemia.Nature cell biology · 2023Article
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Article
- Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.Nature cancer · 2022Article
- A Metabolic Reprogramming Amino Acid Polymer as an Immunosurveillance Activator and Leukemia Targeting Drug Carrier for T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia.The Journal of clinical investigation · 2021Article
- Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia.Haematologica · 2021Article
- Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.PLoS genetics · 2021Article
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Reactive oxygen species (ROS), a byproduct of cellular metabolism, damage intracellular macromolecules and, when present in excess, can promote normal hematopoietic stem cell differentiation and exhaustion. However, mechanisms that regulate the amount of ROS in leukemia-initiating cells (LICs) and the biological role of ROS in these cells are largely unknown. We show here that the ROS(low) subset of CD44(+) cells in T cell acute lymphoblastic leukemia (T-ALL), a malignancy of immature T cell progenitors, is highly enriched in the most aggressive LICs and that ROS accumulation is restrained by downregulation of protein kinase C θ (PKC-θ). Notably, primary mouse T-ALLs lacking PKC-θ show improved LIC activity, whereas enforced PKC-θ expression in both mouse and human primary T-ALLs compromised LIC activity. We also show that PKC-θ is regulated by a new pathway in which NOTCH1 induces runt-related transcription factor 3 (RUNX3), RUNX3 represses RUNX1 and RUNX1 induces PKC-θ. NOTCH1, which is frequently activated by mutation in T-ALL and required for LIC activity in both mouse and human models, thus acts to repress PKC-θ. These results reveal key functional roles for PKC-θ and ROS in T-ALL and suggest that aggressive biological behavior in vivo could be limited by therapeutic strategies that promote PKC-θ expression or activity, or the accumulation of ROS.
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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.