Cited by 284Neurofibromatosis and Schwannoma CasesProtein Tyrosine PhosphatasesAcute Myeloid Leukemia Research

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Nf1 deficiency causes Ras-Dediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia

Largaespada, David A., Brannan, Camilynn I., Jenkins, Nancy A., Copeland, Neal G.·1996·Nature Genetics

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Abstract

The Ras signal transduction pathway is often deregulated in human myeloid leukaemia. For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase activating protein. By generating mice whose haematopoietic system is reconsituted with Nf1 deficient haematopoietic stem cells we show that Nf1 gene loss, by itself, is sufficient to produce the myeloproliferative symptoms associated with human JCML. We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF). Finally, we describe a genetic screen for identifying genes that cooperate with Nf1 gene loss during progression to acute myeloid leukaemia.

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Authors: Largaespada, D. A., Brannan, C. I., Jenkins, N. A., & Copeland, N. G.
Affiliations: Frederick National Laboratory for Cancer Research (US)
University of Florida (US)
ORCID: Largaespada, David A.
Jenkins, Nancy A.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1996-02
Volume: 12
Issue: 2
Pages: 137-143
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0296-137
OpenAlex: W2087533846
Cited by: 284
References: 33
Citations by year: 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 14
FWCI: 15.71
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords: neurofibromatosis type 1, NF1 deficiency, Ras signaling, GM-CSF, GM-CSF hypersensitivity, chronic myeloid leukemia, myeloproliferative neoplasms, hematopoietic stem cells, genetic screen, Ras GTPase-activating protein
MeSH terms: Acute Disease, Animals, Bone Marrow, Cell Differentiation, Cell Line, Transformed, Crosses, Genetic, Disease Models, Animal, Female, Guanosine Triphosphate, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Liver, Male, Mice, Inbred C57BL, Signal Transduction, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Granulocyte-Macrophage Colony-Stimulating Factor, Genes, Neurofibromatosis 1, Hematopoietic Stem Cell Transplantation, Disease Progression, ras Proteins, Mice

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Nf1 deficiency causes Ras-Dediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia

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