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 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

Blood

journal_title

Blood

authors

Cheng K,Sportoletti P,Ito K,Clohessy JG,Teruya-Feldstein J,Kutok JL,Pandolfi PP

doi

10.1182/blood-2009-03-208587

subject

Has Abstract

pub_date

2010-04-22 00:00:00

pages

3341-5

issue

16

eissn

0006-4971

issn

1528-0020

pii

blood-2009-03-208587

journal_volume

115

pub_type

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