ArticleBlood2010
Deletion-based mechanisms of Notch1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in Notch1.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 91 citations in OpenAlex.
- Safety, Feasibility, and Merits of Longitudinal Molecular Testing of Multiple Metastatic Sites to Inform mTNBC Patient Treatment in the Intensive Trial of Omics in Cancer.JCO precision oncology · 2022Trial
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- Functional and molecular single-cell analyses implicate PRDM14 in the initiation of B cell leukemia in mice.Scientific reports · 2025Article
- NOTCH1 fusions in pediatric T-cell lymphoblastic lymphoma: A high-risk subgroup with CCL17 (TARC) levels as diagnostic biomarker.HemaSphere · 2024Article
- IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Inhibition of the NOTCH and mTOR pathways by nelfinavir as a novel treatment for T cell acute lymphoblastic leukemia.International journal of oncology · 2023Article
- Outlier Expression of Isoforms by Targeted or Total RNA Sequencing Identifies Clinically Significant Genomic Variants in Hematolymphoid Tumors.The Journal of molecular diagnostics : JMD · 2023Article
- Article
- A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and β-selection.Nature immunology · 2022Article
- Interleukin-7 receptor signaling is crucial for enhancer-dependent TCRδ germline transcription mediated through STAT5 recruitment.Frontiers in immunology · 2022Article
- E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Review
- MonoallelicFrontiers in immunology · 2022Article
- Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 inFrontiers in immunology · 2022Article
- 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
- Genome-Wide Analysis IdentifiesFrontiers in cell and developmental biology · 2021Article
- Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice.Veterinary pathology · 2020Article
- A unique mutator phenotype reveals complementary oncogenic lesions leading to acute leukemia.JCI insight · 2019Article
- Therapeutic targeting of Notch signaling and immune checkpoint blockade in a spontaneous, genetically heterogeneous mouse model of T-cell acute lymphoblastic leukemia.Disease models & mechanisms · 2019Article
- KDM2B in polycomb repressive complex 1.1 functions as a tumor suppressor in the initiation of T-cell leukemogenesis.Blood advances · 2019Article
- The Pluripotency Regulator PRDM14 Requires Hematopoietic Regulator CBFA2T3 to Initiate Leukemia in Mice.Molecular cancer research : MCR · 2019Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Point mutations that trigger ligand-independent proteolysis of the Notch1 ectodomain occur frequently in human T-cell acute lymphoblastic leukemia (T-ALL) but are rare in murine T-ALL, suggesting that other mechanisms account for Notch1 activation in murine tumors. Here we show that most murine T-ALLs harbor Notch1 deletions that fall into 2 types, both leading to ligand-independent Notch1 activation. Type 1 deletions remove exon 1 and the proximal promoter, appear to be RAG-mediated, and are associated with mRNA transcripts that initiate from 3' regions of Notch1. In line with the RAG dependency of these rearrangements, RAG2 binds to the 5' end of Notch1 in normal thymocytes near the deletion breakpoints. Type 2 deletions remove sequences between exon 1 and exons 26 to 28 of Notch1, appear to be RAG-independent, and are associated with transcripts in which exon 1 is spliced out of frame to 3' Notch1 exons. Translation of both types of transcripts initiates at a conserved methionine residue, M1727, which lies within the Notch1 transmembrane domain. Polypeptides initiating at M1727 insert into membranes and are subject to constitutive cleavage by γ-secretase. Thus, like human T-ALL, murine T-ALL is often associated with acquired mutations that cause ligand-independent Notch1 activation.
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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.