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
Language
- eng
Conference Location
- United States