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

2003; National Academy of Sciences; Volume: 101; Issue: 2 Linguagem: Inglês

10.1073/pnas.0307203101

1091-6490

Benjamin S. Braun, David A. Tuveson, Namie Kong, Doan Le, Scott C. Kogan, Jacob Rozmus, Michelle M. Le Beau, Tyler Jacks, Kevin Shannon,

Retinoids in leukemia and cellular processes

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.