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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4269-4277. Prepublished online as a Blood First Edition Paper on August 16, 2005; DOI 10.1182/blood-2005-04-1679. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-04-1679v1 106/13/4269    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 Kawagoe, H. Articles by Grosveld, G. C. Search for Related Content PubMed PubMed Citation Articles by Kawagoe, H. Articles by Grosveld, G. C. Related Collections Neoplasia Oncogenes and Tumor Suppressors Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9 Hiroyuki Kawagoe, and Gerard C. Grosveld From the Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN. The chromosomal translocation t(12; 22)(p13;q11) in human myeloid leukemia generates an MN1-TEL (meningioma 1-translocation-ETS-leukemia) fusion oncoprotein. This protein consists of N-terminal MN1 sequences, a transcriptional coactivator fused to C-terminal TEL sequences, an ETS (E26 transformation-specific) transcription factor. Enforced expression of MN1-TEL in multipotent hematopoietic progenitors in knock-in mice perturbed growth and differentiation of myeloid as well as lymphoid cells. Depending on obligatory secondary mutations, these mice developed T-cell lympholeukemia. Here we addressed the role of MN1-TEL in myeloid leukemogenesis using the same mouse model. Expression of MN1-TEL enhanced the growth of myeloid progenitors in an interleukin 3/stem cell factor (IL-3/SCF)–dependent manner in vitro whereas 10% of MN1-TEL–expressing mice developed altered myelopoiesis with severe anemia after long latency. Coexpression of MN1-TEL and IL-3, but not SCF, rapidly caused a fatal myeloproliferative disease rather than acute myeloid leukemia (AML). Because MN1-TEL+ AML patient cells overexpress HOXA9 (homeobox A9), we tested the effect of coexpression of MN1-TEL and HOXA9 in mice and found that 90% of MN1-TEL+/HOXA9+ mice developed AML much more rapidly than control HOXA9+ mice. Thus, the leukemogenic effect of MN1-TEL in our knock-in mice is pleiotropic, and the type of secondary mutation determines disease outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both myeloid and lymphoid growth and causes T-lymphoid tumors in mice Hiroyuki Kawagoe and Gerard C. Grosveld Blood 2005 106: 4278-4286. [Abstract] [Full Text] [PDF] This article has been cited by other articles: H. Kawagoe, A. Kandilci, T. A. Kranenburg, and G. C. Grosveld Overexpression of N-Myc Rapidly Causes Acute Myeloid Leukemia in Mice Cancer Res., November 15, 2007; 67(22): 10677 - 10685. [Abstract] [Full Text] [PDF] G. C. Grosveld Treating AML with ATRA? Beware MN1! Blood, September 1, 2007; 110(5): 1401 - 1402. [Full Text] [PDF] M. Heuser, B. Argiropoulos, F. Kuchenbauer, E. Yung, J. Piper, S. Fung, R. F. Schlenk, K. Dohner, T. Hinrichsen, C. Rudolph, et al. MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML Blood, September 1, 2007; 110(5): 1639 - 1647. [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] M. A Meester-Smoor, A. C Molijn, Y. Zhao, N. A Groen, C. A H Groffen, M. Boogaard, D. van Dalsum-Verbiest, G. C Grosveld, and E. C Zwarthoff The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence J. Mol. Endocrinol., January 1, 2007; 38(1): 113 - 125. [Abstract] [Full Text] [PDF] M. Heuser, G. Beutel, J. Krauter, K. Dohner, N. von Neuhoff, B. Schlegelberger, and A. Ganser High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics Blood, December 1, 2006; 108(12): 3898 - 3905. [Abstract] [Full Text] [PDF] H. Kawagoe and G. C. Grosveld MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both myeloid and lymphoid growth and causes T-lymphoid tumors in mice Blood, December 15, 2005; 106(13): 4278 - 4286. [Abstract] [Full Text] [PDF]

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