ArticleThe Journal of clinical investigation2008
Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 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
148 citing papers in PubMed, 229 citations in OpenAlex.
- Trial
- Trial
- Direct pharmacological targeting of asparagine synthetase to overcome resistance to L-asparaginase in ALL therapy.JCI insight · 2026Article
- c-Medical sciences (Basel, Switzerland) · 2026Review
- Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes.eLife · 2025Article
- Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025Review
- FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia.Science advances · 2025Article
- BCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2024Article
- BIRC5 upregulation enhances DNMT3A-mutant T-ALL cell survival and pathogenesis.Blood neoplasia · 2024Article
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Targeted Metabolomics of Tissue and Plasma Identifies Biomarkers in Mice with NOTCH1-Dependent T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Article
- Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.Leukemia · 2024Article
- Collaboration ofFuture science OA · 2024Article
- Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.Blood · 2023Article
- DHODH: a promising target in the treatment of T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.Blood · 2023Article
- Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition.The Journal of experimental medicine · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Gain-of-function NOTCH1 mutations are found in 50%-70% of human T cell acute lymphoblastic leukemia/lymphoma (T-ALL) cases. Gain-of-function NOTCH1 alleles that initiate strong downstream signals induce leukemia in mice, but it is unknown whether the gain-of-function NOTCH1 mutations most commonly found in individuals with T-ALL generate downstream signals of sufficient strength to induce leukemia. We addressed this question by expressing human gain-of-function NOTCH1 alleles of varying strength in mouse hematopoietic precursors. Uncommon gain-of-function NOTCH1 alleles that initiated strong downstream signals drove ectopic T cell development and induced leukemia efficiently. In contrast, although gain-of-function alleles that initiated only weak downstream signals also induced ectopic T cell development, these more common alleles failed to efficiently initiate leukemia development. However, weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition. These data show that induction of leukemia requires doses of Notch1 greater than those needed for T cell development and that most NOTCH1 mutations found in T-ALL cells do not generate signals of sufficient strength to initiate leukemia development. Furthermore, low, nonleukemogenic levels of Notch1 can complement other leukemogenic events, such as activation of K-ras. Even when Notch1 participates secondarily, the resulting tumors show "addiction" to Notch, providing a further rationale for evaluating Notch signaling pathway inhibitors in leukemia.
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.