Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder

Doan T. Le, Namie Kong, Yuan Zhu, Jennifer O. Lauchle, Abigail Aiyigari, Benjamin S. Braun, Endi Wang, Scott C. Kogan, Michelle M. Le Beau, Luis Parada, Kevin M. Shannon

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137 Scopus citations

Abstract

The NF1 tumor suppressor gene encodes a guanosine triphosphotase (GTPase)-activating protein that negatively regulates Ras signaling and is inactivated in a subset of juvenile myelomonocytic leukemias (JMMLs). Adoptive transfer of fetal liver cells from Nf1 mutant mice models JMML; however, this system has important limitations as a platform for performing biologic and preclinical studies. We have exploited the interferon-inducible Mx1-Cre transgene to ablate a conditional mutant Nf1 allele in hematopoietic cells. Somatic inactivation of Nf1 induces a myeloproliferative disorder with 100% penetrance that is associated with a subacute clinical course, tissue infiltration by myeloid cells, hypersensitivity to granulocyte-macrophage colony stimulating factor, hyperproliferation, and resistance to apoptosis. These Mx1-Cre, Nf1flox/flox mice establish a tractable experimental model for testing therapeutics and for identifying mutations that cooperate with hyperactive Ras in myeloid leukemogenesis.

Original languageEnglish (US)
Pages (from-to)4243-4250
Number of pages8
JournalBlood
Volume103
Issue number11
DOIs
StatePublished - Jun 1 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Le, D. T., Kong, N., Zhu, Y., Lauchle, J. O., Aiyigari, A., Braun, B. S., Wang, E., Kogan, S. C., Le Beau, M. M., Parada, L., & Shannon, K. M. (2004). Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood, 103(11), 4243-4250. https://doi.org/10.1182/blood-2003-08-2650