| First Author | Chan IT | Year | 2004 |
| Journal | Cell Cycle | Volume | 3 |
| Issue | 5 | Pages | 536-7 |
| PubMed ID | 15020845 | Mgi Jnum | J:90338 |
| Mgi Id | MGI:3043164 | Doi | 10.4161/cc.3.5.828 |
| Citation | Chan IT, et al. (2004) Oncogenic K-ras in Mouse Models of Myeloproliferative Disease and Acute Myeloid Leukemia. Cell Cycle 3(5):536-7 |
| abstractText | Oncogenic N-RAS and K-RAS mutations are among the most frequently detected genetic alterations in patients with acute myeloid leukemia (AML). Recently, the role of oncogenic K-ras in leukemogenesis was investigated in a novel mouse model utilizing interferon (IFN)-inducible, Cre-mediated expression of oncogenic K-ras from its endogenous promoter. Conditional expression of oncogenic K-ras from its endogenous promoter in the hematopoietic system induces a lethal myeloproliferative disease in mice, but not AML, indicating that additional mutations are required for AML development. These results are consistent with a model in which the AML phenotype requires at least two cooperating mutations in the hematopoietic progenitor cells: one promoting proliferation and enhanced cell survival (such as oncogenic ras or a constitutively activated receptor tyrosine kinase) and one associated with impaired differentiation and enhanced immortalization (such as loss-of-function mutations in hematopoietic transcription factors). The model system with oncogenic K-ras provides a versatile platform to test the contribution of cooperating mutations in AML, and the efficacy of Ras pathway inhibitors in vivo. |
