The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model Journal Article
| Authors: | Cheng, K.; Sportoletti, P.; Ito, K.; Clohessy, J. G.; Teruya-Feldstein, J.; Kutok, J. L.; Pandolfi, P. P. |
| Article Title: | The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model |
| Abstract: | 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 transgenic model (hMRP8-NPM). Interestingly, hMRP8-NPMc+ transgenic mice developed myeloproliferation in bone marrow and spleen, whereas nontransgenic litter-mates 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+. © 2010 by The American Society of Hematology. |
| Keywords: | controlled study; gene mutation; promoter region; mutation; myeloproliferative disorder; leukemia, myeloid, acute; nonhuman; flow cytometry; mutant protein; animal cell; mouse; animals; mice; animal tissue; gene expression; spleen; animal experiment; in vivo study; wild type; mice, inbred c57bl; transgenic mouse; mice, transgenic; nuclear proteins; blotting, western; messenger rna; reverse transcriptase polymerase chain reaction; promoter regions, genetic; leukemogenesis; cytoplasm; hematopoiesis; bone marrow cell; mice, inbred cba; disease models, animal; cell separation; gene expression regulation, leukemic; myeloid cells; calgranulin a; nucleophosmin |
| Journal Title: | Blood |
| Volume: | 115 |
| Issue: | 16 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2010-04-22 |
| Start Page: | 3341 |
| End Page: | 3345 |
| Language: | English |
| DOI: | 10.1182/blood-2009-03-208587 |
| PUBMED: | 19666870 |
| PROVIDER: | scopus |
| PMCID: | PMC2858489 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus" |
