Nf1 and Gmcsf interact in myeloid leukemogenesis

Ron A. Birnbaum, Aengus O'Marcaigh, Zabihullah Wardak, You Yan Zhang, Glenn Dranoff, Tyler Jacks, D. Wade Clapp, Kevin M. Shannon

Research output: Contribution to journalArticle

108 Scopus citations


The NF1 tumor suppressor gene encodes neurofibromin, a GTPase-activating protein (GAP) for p21(ras) (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 plays a central role in establishing and maintaining the MPD and that recipients engrafted with Nf1(-/-) Gmcsf(-/-) hematopoietic cells are hypersensitive to exogenous GM-CSF.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalMolecular Cell
Issue number1
StatePublished - Jan 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Birnbaum, R. A., O'Marcaigh, A., Wardak, Z., Zhang, Y. Y., Dranoff, G., Jacks, T., Clapp, D. W., & Shannon, K. M. (2000). Nf1 and Gmcsf interact in myeloid leukemogenesis. Molecular Cell, 5(1), 189-195.