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

Journal Article (Journal Article)

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 sub-acute clinical course, tissue infiltration by myeloid cells, hypersensitivity to granulocyte-macrophage colony stimulating factor, hyperproliferation, and resistance to apoptosis. These Mx1-Cre, Nf1(flox/flox) mice establish a tractable experimental model for testing therapeutics and for identifying mutations that cooperate with hyperactive Ras in myeloid leukemogenesis.

Full Text

Duke Authors

Cited Authors

  • Le, DT; Kong, N; Zhu, Y; Lauchle, JO; Aiyigari, A; Braun, BS; Wang, E; Kogan, SC; Le Beau, MM; Parada, L; Shannon, KM

Published Date

  • June 1, 2004

Published In

Volume / Issue

  • 103 / 11

Start / End Page

  • 4243 - 4250

PubMed ID

  • 14982883

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2003-08-2650


  • eng

Conference Location

  • United States