Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse Journal Article

Authors: Sportoletti, P.; Grisendi, S.; Majid, S. M.; Cheng, K.; Clohessy, J. G.; Viale, A.; Teruya-Feldstein, J.; Pandolfi, P. P.
Article Title: Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse
Abstract: Nucleophosmin (NPM1) gene has been heavily implicated in cancer pathogenesis both as a putative proto-oncogene and tumor suppressor gene. NPM1 is the most frequently mutated gene in acute myeloid leukemia (AML), while deletion of 5q, where NPM1 maps, is frequent in patients with myelodysplastic syndromes (MDS). We have previously shown that mice heterozygous for Npm1 (Npm1+/- ) develop a hematologic syndrome with features of human MDS. Here we analyzed Npm1+/- mutants to determine their susceptibility to cancer. Npm1+/- mice displayed a greater propensity to develop malignancies compared with Npm1+/+ mice. The Npm1+/- cohort frequently developed hematologic malignancies of both myeloid and lymphoid origin with myeloid malignancies displaying the highest incidence. Malignant cells retained the wild-type allele with normal localization and expression of Npm1 at the protein level, suggesting that complete Npm1 loss is not a prerequisite for tumorigenesis. Our results conclusively demonstrate that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment.© 2008 by The American Society of Hematology.
Keywords: controlled study; protein expression; oncoprotein; acute granulocytic leukemia; gene mutation; genetics; leukemia, myeloid, acute; pathogenesis; nonhuman; cancer incidence; protein localization; mouse; animal; metabolism; animals; mice; allele; animal tissue; cancer susceptibility; proto oncogene; nuclear protein; animal experiment; animal model; alleles; pathology; wild type; carcinogenesis; cell transformation, neoplastic; nuclear proteins; tumor suppressor gene; hematologic malignancy; myelodysplastic syndrome; blood disease; hematologic neoplasms; cell transformation; heterozygosity; oncogene proteins; gene repression; tumor suppressor proteins; lymphoma; hematopoiesis; bone marrow cell; tumor suppressor protein; myelodysplastic syndromes; nucleophosmin; chromosome 5q
Journal Title: Blood
Volume: 111
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2008-04-01
Start Page: 3859
End Page: 3862
Language: English
DOI: 10.1182/blood-2007-06-098251
PUBMED: 18212245
PROVIDER: scopus
PMCID: PMC2275037
Notes: --- - "Cited By (since 1996): 40" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
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