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Blood, 1 July 2005, Vol. 106, No. 1, pp. 287-295. Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2004-12-4794. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2004-12-4794v1 106/1/287    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Lin, Y.-W. Articles by Aplan, P. D. Search for Related Content PubMed PubMed Citation Articles by Lin, Y.-W. Articles by Aplan, P. D. Related Collections Hematopoiesis and Stem Cells Neoplasia Apoptosis Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia Ying-Wei Lin, Christopher Slape, Zhenhua Zhang, and Peter D. Aplan From the Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. The myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis and dysplasia. A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene. Using a NUP98-HOXD13 fusion gene, we have developed a mouse model that faithfully recapitulates all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia, and apoptosis, and transformation to acute leukemia. The MDS that develops in NUP98-HOXD13 transgenic mice is uniformly fatal. Within 14 months, all of the mice died of either leukemic transformation or severe anemia and leucopenia as a result of progressive MDS. The NUP98-HOXD13 fusion gene inhibits megakaryocytic differentiation and increases apoptosis in the bone marrow, suggesting a mechanism leading to ineffective hematopoiesis in the presence of a hypercellular bone marrow. These mice provide an accurate preclinical model that can be used for the evaluation of MDS therapy and biology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. W. Choi, Y. J. Chung, C. Slape, and P. D. Aplan A NUP98-HOXD13 Fusion Gene Impairs Differentiation of B and T Lymphocytes and Leads to Expansion of Thymocytes with Partial TCRB Gene Rearrangement J. Immunol., November 15, 2009; 183(10): 6227 - 6235. [Abstract] [Full Text] [PDF] A. Tefferi and J. W. Vardiman Myelodysplastic Syndromes N. Engl. J. Med., November 5, 2009; 361(19): 1872 - 1885. [Full Text] [PDF] M. Heuser, D. B. Yap, M. Leung, T. R. de Algara, A. Tafech, S. McKinney, J. Dixon, R. Thresher, B. Colledge, M. Carlton, et al. Loss of Mll5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation Blood, February 12, 2009; 113(7): 1432 - 1443. [Abstract] [Full Text] [PDF] Y. J. Chung, C. W. Choi, C. Slape, T. Fry, and P. D. Aplan Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell PNAS, September 16, 2008; 105(37): 14088 - 14093. [Abstract] [Full Text] [PDF] M. Fontenay and E. Gyan Apoptotic pathways to death in myelodysplastic syndromes Haematologica, September 1, 2008; 93(9): 1288 - 1292. [Full Text] [PDF] C. W. Choi, Y. J. Chung, C. Slape, and P. D. Aplan Impaired differentiation and apoptosis of hematopoietic precursors in a mouse model of myelodysplastic syndrome Haematologica, September 1, 2008; 93(9): 1394 - 1397. [Abstract] [Full Text] [PDF] C. Slape, L. Y. Liu, S. Beachy, and P. D. Aplan Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras, and Cbl Blood, September 1, 2008; 112(5): 2017 - 2019. [Abstract] [Full Text] [PDF] C. Slape, Y. W. Lin, H. Hartung, Z. Zhang, L. Wolff, and P. D. Aplan NUP98-HOX Translocations Lead to Myelodysplastic Syndrome in Mice and Men J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 64 - 68. [Abstract] [Full Text] [PDF] D. Jankovic, P. Gorello, T. Liu, S. Ehret, R. La Starza, C. Desjobert, F. Baty, M. Brutsche, P.-S. Jayaraman, A. Santoro, et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia Blood, June 15, 2008; 111(12): 5672 - 5682. [Abstract] [Full Text] [PDF] S. D. Nimer Myelodysplastic syndromes Blood, May 15, 2008; 111(10): 4841 - 4851. [Abstract] [Full Text] [PDF] N. Watanabe-Okochi, J. Kitaura, R. Ono, H. Harada, Y. Harada, Y. Komeno, H. Nakajima, T. Nosaka, T. Inaba, and T. Kitamura AML1 mutations induced MDS and MDS/AML in a mouse BMT model Blood, April 15, 2008; 111(8): 4297 - 4308. [Abstract] [Full Text] [PDF] C. Hoemme, A. Peerzada, G. Behre, Y. Wang, M. McClelland, K. Nieselt, M. Zschunke, C. Disselhoff, S. Agrawal, F. Isken, et al. Chromatin modifications induced by PML-RAR{alpha} repress critical targets in leukemogenesis as analyzed by ChIP-Chip Blood, March 1, 2008; 111(5): 2887 - 2895. [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] D. Caudell, Z. Zhang, Y. J. Chung, and P. D. Aplan Expression of a CALM-AF10 Fusion Gene Leads to Hoxa Cluster Overexpression and Acute Leukemia in Transgenic Mice Cancer Res., September 1, 2007; 67(17): 8022 - 8031. [Abstract] [Full Text] [PDF] C. Slape, H. Hartung, Y.-W. Lin, J. Bies, L. Wolff, and P. D. Aplan Retroviral Insertional Mutagenesis Identifies Genes that Collaborate with NUP98-HOXD13 during Leukemic Transformation Cancer Res., June 1, 2007; 67(11): 5148 - 5155. [Abstract] [Full Text] [PDF] Y. Ma, W. Cui, J. Yang, J. Qu, C. Di, H. M. Amin, R. Lai, J. Ritz, D. S. Krause, and L. Chai SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice Blood, October 15, 2006; 108(8): 2726 - 2735. [Abstract] [Full Text] [PDF] A. Takeda, C. Goolsby, and N. R. Yaseen NUP98-HOXA9 Induces Long-term Proliferation and Blocks Differentiation of Primary Human CD34+ Hematopoietic Cells. Cancer Res., July 1, 2006; 66(13): 6628 - 6637. [Abstract] [Full Text] [PDF] X.-T. Bai, B.-W. Gu, T. Yin, C. Niu, X.-D. Xi, J. Zhang, Z. Chen, and S.-J. Chen Trans-Repressive Effect of NUP98-PMX1 on PMX1-Regulated c-FOS Gene through Recruitment of Histone Deacetylase 1 by FG Repeats. Cancer Res., May 1, 2006; 66(9): 4584 - 4590. [Abstract] [Full Text] [PDF] Y.-W. Lin, R. A. Nichols, J. J. Letterio, and P. D. Aplan Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma Blood, March 15, 2006; 107(6): 2540 - 2543. [Abstract] [Full Text] [PDF] Y.-W. Lin, R. Deveney, M. Barbara, N. N. Iscove, S. D. Nimer, C. Slape, and P. D. Aplan OLIG2 (BHLHB1), a bHLH Transcription Factor, Contributes to Leukemogenesis in Concert with LMO1 Cancer Res., August 15, 2005; 65(16): 7151 - 7158. [Abstract] [Full Text] [PDF]

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