| First Author | Cutts BA | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 17 | Pages | 3629-32 |
| PubMed ID | 19710506 | Mgi Jnum | J:153839 |
| Mgi Id | MGI:4366396 | Doi | 10.1182/blood-2009-02-205146 |
| Citation | Cutts BA, et al. (2009) Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice. Blood 114(17):3629-32 |
| abstractText | Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase-activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS-induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RAS(G12D) in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS. |
