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

Nature Genetics volume 12, pages 137–143 (1996)Cite this article

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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Author notes

  1. Camilynn I. Brannan

    Present address: Department of Molecular Genetics and Microbiology and Center for Mammalian Genetics, University of Florida, P.O. Box 100266, Gainesville, Florida, 32610

Authors and Affiliations

  1. Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702

    David A. Largaespada, Camilynn I. Brannan, Nancy A. Jenkins & Neal G. Copeland

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  1. David A. Largaespada
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  2. Camilynn I. Brannan
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  3. Nancy A. Jenkins
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  4. Neal G. Copeland
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Largaespada, D., Brannan, C., Jenkins, N. et al. Nf1 deficiency causes Ras-Dediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat Genet 12, 137–143 (1996). https://doi.org/10.1038/ng0296-137

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