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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4278-4286. Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-04-1674. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-04-1674v1 106/13/4278    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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 26, 2005 Accepted July 23, 2005 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* Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA * Corresponding author; email: gerard.grosveld{at}stjude.org. The MN1-TEL fusion oncoprotein is the product of the t(12;22)(p13;q11) in human myeloid leukemia, consisting of N-terminal MN1 sequences, a transcriptional co-activator, fused to C-terminal TEL sequences, an ETS transcription factor. To analyze the role of MN1-TEL in leukemogenesis, we created a site-directed transgenic (knock-in) mouse model carrying a conditional MN1-TEL transgene under the control of the Aml1 regulatory sequences. After induction, MN1-TEL expression was detected in both myeloid and lymphoid cells. Activation of MN1-TEL expression enhanced the repopulation ability of myeloid progenitors in-vitro as well as partially inhibited their differentiation in-vivo. MN1-TEL also promoted the proliferation of thymocytes while it blocked their differentiation from CD4-/CD8- to CD4+/CD8+ in-vivo. After long latency, 30% of the MN1-TEL+ mice developed T-lymphoid tumors. This process was accelerated by N-ethyl-N-nitrosourea-induced mutations. MN1-TEL+ T-lymphoid tumors showed elevated expression of the Notch-1, Hes-1, c-Myc and Lmo-2 genes while their Ink4a/pRB and Arf/p53 pathways were impaired, suggesting that these alterations cooperatively transform T-progenitors. We conclude that MN1-TEL exerts its not lineage-specific leukemogenic effects by promoting the growth of primitive progenitors and blocking their differentiation, but cooperative mutations are necessary to fully induce leukemic transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9 Hiroyuki Kawagoe and Gerard C. Grosveld Blood 2005 106: 4269-4277. [Abstract] [Full Text] [PDF] This article has been cited by other articles: X. Zhang, D. R. Dowd, M. C. Moore, T. A. Kranenburg, M. A. Meester-Smoor, E. C. Zwarthoff, and P. N. MacDonald Meningioma 1 Is Required for Appropriate Osteoblast Proliferation, Motility, Differentiation, and Function J. Biol. Chem., July 3, 2009; 284(27): 18174 - 18183. [Abstract] [Full Text] [PDF] W. Liu, Y. Lan, E. Pauws, M. A. Meester-Smoor, P. Stanier, E. C. Zwarthoff, and R. Jiang The Mn1 transcription factor acts upstream of Tbx22 and preferentially regulates posterior palate growth in mice Development, December 1, 2008; 135(23): 3959 - 3968. [Abstract] [Full Text] [PDF] M. Heuser, B. Argiropoulos, F. 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[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 Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9 Blood, December 15, 2005; 106(13): 4269 - 4277. [Abstract] [Full Text] [PDF]

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