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

First Author  Braun BS Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  2 Pages  597-602
PubMed ID  14699048 Mgi Jnum  J:87429
Mgi Id  MGI:2687114 Doi  10.1073/pnas.0307203101
Citation  Braun BS, et al. (2004) Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 101(2):597-602
abstractText  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.
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