ArticleThe Journal of clinical investigation2004
Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.Cancer discovery · 2024Trial
- The Role and Impact of Non-driver Gene Mutations in Myelofibrosis.Current hematologic malignancy reports · 2026Review
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Article
- Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.The Journal of experimental medicine · 2025Article
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Cancerous time estimation for interpreting the evolution of lung adenocarcinoma.Briefings in bioinformatics · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- Article
- Molecular Pathogenesis of Myeloproliferative Neoplasms: From Molecular Landscape to Therapeutic Implications.International journal of molecular sciences · 2022Review
- Murine Models of Acute Myeloid Leukemia.Frontiers in oncology · 2022Review
- Review
- Mouse Models of CMML.International journal of molecular sciences · 2021Review
- Review
- Article
- Micro-RNA-125a mediates the effects of hypomethylating agents in chronic myelomonocytic leukemia.Clinical epigenetics · 2021Article
- Molecular Pathogenesis ofFrontiers in oncology · 2021Review
- Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management.American journal of blood research · 2021Review
- A most formidable arsenal: genetic technologies for building a better mouse.Genes & development · 2020Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
Abstract
Oncogenic ras alleles are among the most common mutations found in patients with acute myeloid leukemia (AML). Previously, the role of oncogenic ras in cancer was assessed in model systems overexpressing oncogenic ras from heterologous promoters. However, there is increasing evidence that subtle differences in gene dosage and regulation of gene expression from endogenous promoters play critical roles in cancer pathogenesis. We characterized the role of oncogenic K-ras expressed from its endogenous promoter in the hematopoietic system using a conditional allele and IFN-inducible, Cre-mediated recombination. Mice developed a completely penetrant myeloproliferative syndrome characterized by leukocytosis with normal maturation of myeloid lineage cells; myeloid hyperplasia in bone marrow; and extramedullary hematopoiesis in the spleen and liver. Flow cytometry confirmed the myeloproliferative phenotype. Genotypic and Western blot analysis demonstrated Cre-mediated excision and expression, respectively, of the oncogenic K-ras allele. Bone marrow cells formed growth factor-independent colonies in methylcellulose cultures, but the myeloproliferative disease was not transplantable into secondary recipients. Thus, oncogenic K-ras induces a myeloproliferative disorder but not AML, indicating that additional mutations are required for AML development. This model system will be useful for assessing the contribution of cooperating mutations in AML and testing ras inhibitors in vivo.
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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 Socratic graph.