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 journalArticle

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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

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Transgenic Mice
Acute Myeloid Leukemia
Mutation
Theoretical Models
Spleen
Bone Marrow
Bone
Genes
Therapeutics
nucleophosmin

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Cheng, K., Sportoletti, P., Ito, K., Clohessy, J. G., Teruya-Feldstein, J., Kutok, J. L., & Pandolfi, P. P. (2010). The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. Blood, 115(16), 3341-3345. https://doi.org/10.1182/blood-2009-03-208587

The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. / Cheng, Ke; Sportoletti, Paolo; Ito, Keisuke; Clohessy, John G.; Teruya-Feldstein, Julie; Kutok, Jeffery L.; Pandolfi, Pier Paolo.

In: Blood, Vol. 115, No. 16, 22.04.2010, p. 3341-3345.

Research output: Contribution to journalArticle

Cheng, K, Sportoletti, P, Ito, K, Clohessy, JG, Teruya-Feldstein, J, Kutok, JL & Pandolfi, PP 2010, 'The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model', Blood, vol. 115, no. 16, pp. 3341-3345. https://doi.org/10.1182/blood-2009-03-208587
Cheng K, Sportoletti P, Ito K, Clohessy JG, Teruya-Feldstein J, Kutok JL et al. The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. Blood. 2010 Apr 22;115(16):3341-3345. https://doi.org/10.1182/blood-2009-03-208587
Cheng, Ke ; Sportoletti, Paolo ; Ito, Keisuke ; Clohessy, John G. ; Teruya-Feldstein, Julie ; Kutok, Jeffery L. ; Pandolfi, Pier Paolo. / The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. In: Blood. 2010 ; Vol. 115, No. 16. pp. 3341-3345.
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