The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model

Ke Cheng, Paolo Sportoletti, Keisuke Ito, John G. Clohessy, Julie Teruya-Feldstein, Jeffery L. Kutok, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

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+.

Original languageEnglish (US)
Pages (from-to)3341-3345
Number of pages5
JournalBlood
Volume115
Issue number16
DOIs
StatePublished - Apr 22 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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