ArticleBlood2010
Acute T-cell leukemias remain dependent on Notch signaling despite PTEN and INK4A/ARF loss.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 91 citations in OpenAlex.
- BCAA catabolism mediates POU2AF1 propionylation to enhance T-ALL development.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.Discover oncology · 2024Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Integrin signaling is critical for myeloid-mediated support of T-cell acute lymphoblastic leukemia.Nature communications · 2023Article
- Dose-Dependent Effects in Plasma Oncotherapy: Critical In Vivo Immune Responses Missed by In Vitro Studies.Biomolecules · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- 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
- Article
- 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
- PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia.Journal of hematology & oncology · 2021Article
- Decitabine inhibits the proliferation of human T-cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway.Oncology letters · 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
- Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia.Experimental hematology & oncology · 2020Review
- Wnt signaling mediates oncogenic synergy between Akt and Dlx5 in T-cell lymphomagenesis by enhancing cholesterol synthesis.Scientific reports · 2020Article
- Synthetic modeling reveals HOXB genes are critical for the initiation and maintenance of human leukemia.Nature communications · 2019Article
- Article
- PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature.Molecular cancer therapeutics · 2017Article
- Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.Experimental hematology · 2017Article
- The homeoprotein Dlx5 drives murine T-cell lymphomagenesis by directly transactivating Notch and upregulating Akt signaling.Oncotarget · 2017Article
- The relevance of PTEN-AKT in relation to NOTCH1-directed treatment strategies in T-cell acute lymphoblastic leukemia.Haematologica · 2016Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
NOTCH1 is activated by mutation in more than 50% of human T-cell acute lymphoblastic leukemias (T-ALLs) and inhibition of Notch signaling causes cell-cycle/growth arrest, providing rationale for NOTCH1 as a therapeutic target. The tumor suppressor phosphatase and tensin homolog (PTEN) is also mutated or lost in up to 20% of cases. It was recently observed among human T-ALL cell lines that PTEN loss correlated with resistance to Notch inhibition, raising concern that patients with PTEN-negative disease may fail Notch inhibitor therapy. As these studies were limited to established cell lines, we addressed this issue using a genetically defined mouse retroviral transduction/bone marrow transplantation model and observed primary murine leukemias to remain dependent on NOTCH1 signaling despite Pten loss, with or without additional deletion of p16(Ink4a)/p19(Arf). We also examined 13 primary human T-ALL samples obtained at diagnosis and found no correlation between PTEN status and resistance to Notch inhibition. Furthermore, we noted in the mouse model that Pten loss accelerated disease onset and produced multiclonal tumors, suggesting NOTCH1 activation and Pten loss may collaborate in leukemia induction. Thus, in contrast to previous findings with established cell lines, these results indicate PTEN loss does not relieve primary T-ALL cells of their "addiction" to Notch signaling.
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