Nf1 and Gmcsf interact in myeloid leukemogenesis

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

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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
Pages (from-to)189-195
Number of pages7
JournalMolecular Cell
Volume5
Issue number1
StatePublished - Jan 2000

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Granulocyte-Macrophage Colony-Stimulating Factor
Myeloproliferative Disorders
Juvenile Myelomonocytic Leukemia
Neurofibromin 1
Proto-Oncogene Proteins p21(ras)
GTPase-Activating Proteins
Methylcellulose
Adoptive Transfer
Tumor Suppressor Genes
Cell Proliferation
Liver

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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

Nf1 and Gmcsf interact in myeloid leukemogenesis. / Birnbaum, Ron A.; O'Marcaigh, Aengus; Wardak, Zabihullah; Zhang, You Yan; Dranoff, Glenn; Jacks, Tyler; Clapp, D.; Shannon, Kevin M.

In: Molecular Cell, Vol. 5, No. 1, 01.2000, p. 189-195.

Research output: Contribution to journalArticle

Birnbaum, RA, O'Marcaigh, A, Wardak, Z, Zhang, YY, Dranoff, G, Jacks, T, Clapp, D & Shannon, KM 2000, 'Nf1 and Gmcsf interact in myeloid leukemogenesis', Molecular Cell, vol. 5, no. 1, pp. 189-195.
Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, Jacks T et al. Nf1 and Gmcsf interact in myeloid leukemogenesis. Molecular Cell. 2000 Jan;5(1):189-195.
Birnbaum, Ron A. ; O'Marcaigh, Aengus ; Wardak, Zabihullah ; Zhang, You Yan ; Dranoff, Glenn ; Jacks, Tyler ; Clapp, D. ; Shannon, Kevin M. / Nf1 and Gmcsf interact in myeloid leukemogenesis. In: Molecular Cell. 2000 ; Vol. 5, No. 1. pp. 189-195.
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