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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3859-3862. Prepublished online as a Blood First Edition Paper on January 22, 2008; DOI 10.1182/blood-2007-06-098251. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-098251v1 111/7/3859    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sportoletti, P. Articles by Pandolfi, P. P. Search for Related Content PubMed PubMed Citation Articles by Sportoletti, P. Articles by Pandolfi, P. P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 28, 2007 Accepted January 13, 2008 Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse Paolo Sportoletti, Silvia Grisendi, Samia M Majid, Ke Cheng, John G Clohessy, Agnes Viale, Julie Teruya-Feldstein, and Pier Paolo Pandolfi* Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, United States Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, United States * Corresponding author; email: ppandolf{at}bidmc.harvard.edu. 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 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 hematological 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 hematological 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Tefferi and J. W. Vardiman Myelodysplastic Syndromes N. Engl. J. Med., November 5, 2009; 361(19): 1872 - 1885. [Full Text] [PDF] O. Kosmider, V. Gelsi-Boyer, M. Cheok, S. Grabar, V. Della-Valle, F. Picard, F. Viguie, B. Quesnel, O. Beyne-Rauzy, E. Solary, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs) Blood, October 8, 2009; 114(15): 3285 - 3291. [Abstract] [Full Text] [PDF] C. Haferlach, C. Mecucci, S. Schnittger, A. Kohlmann, M. Mancini, A. Cuneo, N. Testoni, G. Rege-Cambrin, A. Santucci, M. Vignetti, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features Blood, October 1, 2009; 114(14): 3024 - 3032. [Abstract] [Full Text] [PDF] A. Liso, F. Castiglione, A. Cappuccio, F. Stracci, R. F. Schlenk, S. Amadori, C. Thiede, S. Schnittger, P. J.M. Valk, K. Dohner, et al. A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1) Haematologica, August 1, 2008; 93(8): 1219 - 1226. [Abstract] [Full Text] [PDF] S. D. Nimer MDS: A Stem Cell Disorder--But What Exactly Is Wrong with the Primitive Hematopoietic Cells in This Disease? Hematology, January 1, 2008; 2008(1): 43 - 51. [Abstract] [Full Text] [PDF]

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