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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 (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 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 18, 2005 Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9 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 chromosomal translocation t(12;22)(p13;q11) in human myeloid leukemia generates an MN1-TEL fusion oncoprotein. This protein consists of N-terminal MN1 sequences, a transcriptional co-activator, fused to C-terminal TEL sequences, an ETS 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 lympho-leukemia. 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 IL-3/SCF-dependent manner in-vitro while 10% of MN1-TEL-expressing mice developed altered myelopoiesis with severe anemia after long latency. Co-expression 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, 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? 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