Nf1 and Gmcsf interact in myeloid leukemogenesis

Mol Cell. 2000 Jan;5(1):189-95. doi: 10.1016/s1097-2765(00)80415-3.


The NF1 tumor suppressor gene encodes neurofibromin, a GTPase-activating protein (GAP) for p21ras (Ras). Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML). Some heterozygous Nf1 mutant mice develop a similar myeloproliferative disorder (MPD), and adoptive transfer of Nf1-deficient fetal liver cells consistently induces this MPD. Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures. We generated hematopoietic cells deficient in both Nf1 and Gmcsf to test whether GM-CSF is required to drive excessive proliferation of Nf1-/- cells in vivo. Here we show that GM-CSF play a central role in establishing and maintaining the MPD and that recipients engrafted with Nf1-/- Gmcsf-/- hematopoietic cells are hypersensitive to exogenous GM-CSF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Division
  • Child
  • Crosses, Genetic
  • Female
  • Genes, Neurofibromatosis 1*
  • Genetic Predisposition to Disease
  • Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Heterozygote
  • Humans
  • Leukemia, Myelomonocytic, Chronic / genetics*
  • Leukemia, Myelomonocytic, Chronic / pathology
  • Liver / embryology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mice, Knockout
  • Neurofibromin 1
  • Proteins / genetics*


  • Neurofibromin 1
  • Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor