Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder

BS Braun, DA Tuveson, N Kong… - Proceedings of the …, 2004 - National Acad Sciences
BS Braun, DA Tuveson, N Kong, DT Le, SC Kogan, J Rozmus, MM Le Beau, TE Jacks
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
RAS mutations are common in myeloid malignancies; however, it is not known whether
oncogenic RAS can initiate leukemia. We show that expressing mutant K-RasG12D 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 …
RAS mutations are common in myeloid malignancies; however, it is not known whether oncogenic RAS can initiate leukemia. We show that expressing mutant K-RasG12D 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.
National Acad Sciences