Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder
| Autor: | Namie Kong, David A. Tuveson, Tyler Jacks, Michelle M. Le Beau, Scott C. Kogan, Benjamin S. Braun, Doan T. Le, Kevin Shannon, Jacob Rozmus |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Myeloproliferative Disorders
Multidisciplinary Myeloid Effector Somatic cell Kinase Bone Marrow Cells Biological Sciences Biology Flow Cytometry medicine.disease medicine.disease_cause Mice Haematopoiesis Leukemia Genes ras medicine.anatomical_structure Karyotyping Cancer research medicine Animals KRAS |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:597-602 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0307203101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|