ArticleThe Journal of experimental medicine1998
Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines.
Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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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
63 citing papers in PubMed, 151 citations in OpenAlex.
- NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sequential in vivo CRISPR screens identify the clonal dominance ofBlood science (Baltimore, Md.) · 2026Article
- Systemic skewing of peripheral blood leukocyte composition in neurofibromatosis type 1.Frontiers in immunology · 2026Article
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma.Cancer biology & therapy · 2023Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Role of nerves in neurofibromatosis type 1-related nervous system tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- Review
- Review
- Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference.Neuro-oncology · 2020Article
- Recent advances in genetic predisposition to pediatric acute lymphoblastic leukemia.Expert review of hematology · 2020Review
- Immune profiling of NF1-associated tumors reveals histologic subtype distinctions and heterogeneity: implications for immunotherapy.Oncotarget · 2017Article
- Pak2 regulates myeloid-derived suppressor cell development in mice.Blood advances · 2017Article
- The role of the immune system in neurofibromatosis type 1-associated nervous system tumors.CNS oncology · 2017Review
- Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency.Haematologica · 2016Article
- Loss of neurofibromin Ras-GAP activity enhances the formation of cardiac blood islands in murine embryos.eLife · 2015Article
- Pak2 regulates hematopoietic progenitor cell proliferation, survival, and differentiation.Stem cells (Dayton, Ohio) · 2015Article
- Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase.Nature neuroscience · 2014Article
- Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke.BMC cancer · 2014Article
3 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
7 authors at 3 institutions in 1 country.
Funding
Abstract
Neurofibromin, the protein encoded by the NF1 tumor-suppressor gene, negatively regulates the output of p21(ras) (Ras) proteins by accelerating the hydrolysis of active Ras-guanosine triphosphate to inactive Ras-guanosine diphosphate. Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile chronic myelogenous leukemia (JCML) and other malignant myeloid disorders, and heterozygous Nf1 knockout mice spontaneously develop a myeloid disorder that resembles JCML. Both human and murine leukemias show loss of the normal allele. JCML cells and Nf1-/- hematopoietic cells isolated from fetal livers selectively form abnormally high numbers of colonies derived from granulocyte-macrophage progenitors in cultures supplemented with low concentrations of granulocyte-macrophage colony stimulating factor (GM-CSF). Taken together, these data suggest that neurofibromin is required to downregulate Ras activation in myeloid cells exposed to GM-CSF. We have investigated the growth and proliferation of purified populations of hematopoietic progenitor cells isolated from Nf1 knockout mice in response to the cytokines interleukin (IL)-3 and stem cell factor (SCF), as well as to GM-CSF. We found abnormal proliferation of both immature and lineage-restricted progenitor populations, and we observed increased synergy between SCF and either IL-3 or GM-CSF in Nf1-/- progenitors. Nf1-/- fetal livers also showed an absolute increase in the numbers of immature progenitors. We further demonstrate constitutive activation of the Ras-Raf-MAP (mitogen-activated protein) kinase signaling pathway in primary c-kit+ Nf1-/- progenitors and hyperactivation of MAP kinase after growth factor stimulation. The results of these experiments in primary hematopoietic cells implicate Nf1 as playing a central role in regulating the proliferation and survival of primitive and lineage-restricted myeloid progenitors in response to multiple cytokines by modulating Ras output.
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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.