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Blood, 1 September 2008, Vol. 112, No. 5, pp. 2017-2019. Prepublished online as a Blood First Edition Paper on June 19, 2008; DOI 10.1182/blood-2008-01-135186. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-01-135186v1 112/5/2017    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 Slape, C. Articles by Aplan, P. D. Search for Related Content PubMed PubMed Citation Articles by Slape, C. Articles by Aplan, P. D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 23, 2008 Accepted June 4, 2008 Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras, and Cbl Christopher Slape, Leah Y Liu, Sarah Beachy, and Peter D. Aplan* Genetics Branch, Center for Cancer Research, NCI,NIH, Bethesda, MD, United States * Corresponding author; email: aplanp{at}mail.nih.gov. The NUP98-HOXD13 (NHD13) fusion gene occurs in patients with myelodysplastic syndrome (MDS) and acute non-lymphocytic leukemia (ANLL). We reported that transgenic mice expressing NHD13 develop MDS, and that over half of these mice eventually progress to acute leukemia. The latency period suggests a requirement for at least one complementary event prior to leukemic transformation. We conducted a candidate gene search for complementary events focused on genes that are frequently mutated in human myeloid leukemia. We investigated 22 ANLL samples and found a high frequency of Nras and Kras mutations, an absence of Npm1, p53, Runx1, Kit and Flt3 mutations, and a single Cbl mutation. Our findings support a working hypothesis which predicts that ANLL cases have one mutation which inhibits differentiation, and a complementary mutation which enhances proliferation or inhibit apoptosis. In addition, we provide the first evidence for spontaneous collaborating mutations in a genetically engineered mouse model of ANLL. 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] S. R. Bandi, C. Brandts, M. Rensinghoff, R. Grundler, L. Tickenbrock, G. Kohler, J. Duyster, W. E. Berdel, C. Muller-Tidow, H. Serve, et al. E3 ligase-defective Cbl mutants lead to a generalized mastocytosis and myeloproliferative disease Blood, November 5, 2009; 114(19): 4197 - 4208. [Abstract] [Full Text] [PDF] F. H. Grand, C. E. Hidalgo-Curtis, T. Ernst, K. Zoi, C. Zoi, C. McGuire, S. Kreil, A. Jones, J. Score, G. Metzgeroth, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms Blood, June 11, 2009; 113(24): 6182 - 6192. [Abstract] [Full Text] [PDF] J. V. Abella and M. Park Breakdown of endocytosis in the oncogenic activation of receptor tyrosine kinases Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E973 - E984. [Abstract] [Full Text] [PDF]

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