ArticleBlood2008
K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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
63 citing papers in PubMed, 95 citations in OpenAlex.
- Decoding NOTCH1: From T-Cell Development Guardian to Driver of Pediatric T-Cell Lymphoblastic Lymphoma.International journal of molecular sciences · 2026Review
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Pre-TCR-targeted immunotherapy for T cell acute lymphoblastic leukemia.Nature immunology · 2025Article
- Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.NPJ precision oncology · 2024Article
- S1P-S1PR3-RAS promotes the progression of S1PR3Leukemia · 2023Article
- Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma.Blood science (Baltimore, Md.) · 2023Article
- Pdx1 expression in hematopoietic cells activatesLeukemia & lymphoma · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders.Cancers · 2022Review
- Reposition of the anti-inflammatory drug diacerein in anSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Development of thymic tumor in [LSL:KrasScientific reports · 2021Article
- Article
- Point Mutation Specific Antibodies in B-Cell and T-Cell Lymphomas and Leukemias: Targeting IDH2, KRAS, BRAF and Other Biomarkers RHOA, IRF8, MYD88, ID3, NRAS, SF3B1 and EZH2.Diagnostics (Basel, Switzerland) · 2021Review
- Protein Kinases in Hematological Disorders.Advances in experimental medicine and biology · 2021Review
- Lipid composition of the cancer cell membrane.Journal of bioenergetics and biomembranes · 2020Review
- Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment.Frontiers in pediatrics · 2020Article
- IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia.Blood · 2019Article
- Downregulating Notch counteracts KrasLeukemia · 2019Article
- The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model.The Journal of clinical investigation · 2018Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to gamma-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways.
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.