ArticleLeukemia2015
Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- TGFCells · 2023Article
- T-ALL can evolve to oncogene independence.Leukemia · 2021Article
- The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.Cancer reports (Hoboken, N.J.) · 2021Review
- Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma.Cancer research · 2021Article
- The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies.Frontiers in oncology · 2021Review
- NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2020Article
- Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on next‑generation sequencing.Molecular medicine reports · 2019Article
- Article
- Ikaros family zinc finger 1 regulates dendritic cell development and function in humans.Nature communications · 2018Article
- Germline IKAROS mutation associated with primary immunodeficiency that progressed to T-cell acute lymphoblastic leukemia.Leukemia · 2017Article
- Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome.The Journal of experimental medicine · 2017Article
- Notch signalling in context.Nature reviews. Molecular cell biology · 2016Review
- Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.Current opinion in hematology · 2016Review
- PRDM14 promotes RAG-dependent Notch1 driver mutations in mouse T-ALL.Biology open · 2016Article
- Article
- Article
- Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor.Genes & development · 2015Article
- Alternative Splice Variants Modulates Dominant-Negative Function of Helios in T-Cell Leukemia.PloS oneArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Activating NOTCH1 mutations occur in ~60% of human T-cell acute lymphoblastic leukemias (T-ALLs), and mutations disrupting the transcription factor IKZF1 (IKAROS) occur in ~5% of cases. To investigate the regulatory interplay between these driver genes, we have used a novel transgenic RNA interference mouse model to produce primary T-ALLs driven by reversible Ikaros knockdown. Restoring endogenous Ikaros expression in established T-ALL in vivo acutely represses Notch1 and its oncogenic target genes including Myc, and in multiple primary leukemias causes disease regression. In contrast, leukemias expressing high levels of endogenous or engineered forms of activated intracellular Notch1 (ICN1) resembling those found in human T-ALL rapidly relapse following Ikaros restoration, indicating that ICN1 functionally antagonizes Ikaros in established disease. Furthermore, we find that IKAROS mRNA expression is significantly reduced in a cohort of primary human T-ALL patient samples with activating NOTCH1/FBXW7 mutations, but is upregulated upon acute inhibition of aberrant NOTCH signaling across a panel of human T-ALL cell lines. These results demonstrate for the first time that aberrant NOTCH activity compromises IKAROS function in mouse and human T-ALL, and provide a potential explanation for the relative infrequency of IKAROS gene mutations in human T-ALL.
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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.