ArticleBlood2011
Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 97 citations in OpenAlex.
- Very Long Chain Fatty Acid Synthesis is a Targetable Dependency in RAS Pathway Mutant Leukemia.Blood cancer discovery · 2026Article
- Clinical implications of RAS mutations in AML: prognostic significance is based upon the involved gene and mutation complexity.Blood advances · 2026Article
- The m6A methyltransferase METTL14 promotes oncogenic Kras induced juvenile myelomonocytic leukemia through dysregulating autophagy.Cell death and differentiation · 2026Article
- [Chronic myelomonocytic leukemia complicated with T-lymphoblastic lymphoma: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Loss of Golga7 Suppresses Oncogenic Nras-Driven Leukemogenesis without Detectable Toxicity in Adult Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage.Cell death & disease · 2025Article
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- Mutational cooperativity of RUNX1::RUNX1T1 isoform 9a and oncogenic NRAS in zebrafish myeloid leukaemia.Biology open · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice.The Journal of clinical investigation · 2023Article
- RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia.The Journal of clinical investigation · 2023Article
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- Proliferation and Self-Renewal Are Differentially Sensitive to NRASG12V Oncogene Levels in an Acute Myeloid Leukemia Cell Line.Molecular cancer research : MCR · 2022Article
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- Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated hematopoietic dysregulation.Disease models & mechanisms · 2022Article
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- KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders.Cancers · 2022Review
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- Review
12 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
Both monoallelic and biallelic oncogenic NRAS mutations are identified in human leukemias, suggesting a dose-dependent role of oncogenic NRAS in leukemogenesis. Here, we use a hypomorphic oncogenic Nras allele and a normal oncogenic Nras allele (Nras G12D(hypo) and Nras G12D, respectively) to create a gene dose gradient ranging from 25% to 200% of endogenous Nras G12D/+. Mice expressing Nras G12D(hypo)/G12D(hypo) develop normally and are tumor-free, whereas early embryonic expression of Nras G12D/+ is lethal. Somatic expression of Nras G12D/G12D but not Nras G12D/+ leads to hyperactivation of ERK, excessive proliferation of myeloid progenitors, and consequently an acute myeloproliferative disease. Using a bone marrow transplant model, we previously showed that ∼ 95% of animals receiving Nras G12D/+ bone marrow cells develop chronic myelomonocytic leukemia (CMML), while ∼ 8% of recipients develop acute T-cell lymphoblastic leukemia/lymphoma [TALL] (TALL-het). Here we demonstrate that 100% of recipients transplanted with Nras G12D/G12D bone marrow cells develop TALL (TALL-homo). Although both TALL-het and -homo tumors acquire Notch1 mutations and are sensitive to a γ-secretase inhibitor, endogenous Nras G12D/+ signaling promotes TALL through distinct genetic mechanism(s) from Nras G12D/G12D. Our data indicate that the tumor transformation potential of endogenous oncogenic Nras is both dose- and cell type-dependent.
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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.