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

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

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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Crossref · 10.1038/ng0296-137

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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)
Venue
Nature Genetics
Published
1996-02
Volume
12
Issue
2
Pages
137-143
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
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
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › 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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