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 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(+).
journal_name
Bloodjournal_title
Bloodauthors
Cheng K,Sportoletti P,Ito K,Clohessy JG,Teruya-Feldstein J,Kutok JL,Pandolfi PPdoi
10.1182/blood-2009-03-208587subject
Has Abstractpub_date
2010-04-22 00:00:00pages
3341-5issue
16eissn
0006-4971issn
1528-0020pii
blood-2009-03-208587journal_volume
115pub_type
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