Authors:
BS Braun, DA Tuveson, N Kong, DT Le, SC Kogan, J Rozmus, MM Le Beau, TE Jacks, KM Shannon
Journal name: 
Proc Natl Acad Sci U S A
Citation info: 
101(2):597-602
Abstract: 
RAS mutations are common in myeloid malignancies; however, it is not known whether oncogenic RAS can initiate leukemia. We show that expressing mutant K-Ras(G12D) protein from the endogenous murine locus rapidly induces a fatal myeloproliferative disorder with 100% penetrance characterized by tissue infiltration, hypersensitivity to growth factors, and hyperproliferation. Hematopoietic cells from diseased mice demonstrated increased levels of Ras-GTP, but effector kinases were not constitutively phosphorylated and responded normally to growth factors. Oncogenic RAS is sufficient to initiate myeloid leukemogenesis in mice, and this provides an in vivo system for biologic and preclinical studies.
DOI: 
http://doi.org/10.1073/pnas.0307203101
Research group: 
Tuveson Group
E-pub date: 
31 Dec 2003