| First Author | Cheng K | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 16 | Pages | 3341-5 |
| PubMed ID | 19666870 | Mgi Jnum | J:160805 |
| Mgi Id | MGI:4455122 | Doi | 10.1182/blood-2009-03-208587 |
| Citation | Cheng K, et al. (2010) The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. Blood 115(16):3341-5 |
| abstractText | Although NPM1 gene mutations leading to aberrant cytoplasmic expression of nucleophosmin (NPMc(+)) are the most frequent genetic lesions in acute myeloid leukemia, there is yet no experimental model demonstrating their oncogenicity in vivo. We report the generation and characterization of a transgenic mouse model expressing the most frequent human NPMc(+) mutation driven by the myeloid-specific human MRP8 promoter (hMRP8-NPMc(+)). In parallel, we generated a similar wild-type NPM trans-genic model (hMRP8-NPM). Interestingly, hMRP8-NPMc(+) transgenic mice developed myeloproliferation in bone marrow and spleen, whereas nontransgenic littermates and hMRP8-NPM transgenic mice remained disease free. These findings provide the first in vivo evidence indicating that NPMc(+) confers a proliferative advantage in the myeloid lineage. No spontaneous acute myeloid leukemia was found in hMPR8-NPMc(+) or hMRP8-NPM mice. This model will also aid in the development of therapeutic regimens that specifically target NPMc(+). |
