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Blood, 1 July 2005, Vol. 106, No. 1, pp. 254-264. Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2004-12-4664. This Article Full Text (PDF) Supplemental Document All Versions of this Article: 2004-12-4664v1 106/1/254    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 Wang, G. G Articles by Kamps, M. P Search for Related Content PubMed PubMed Citation Articles by Wang, G. G Articles by Kamps, M. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 7, 2004 Accepted February 26, 2005 Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with PBX and a novel function of the Meis1 C-terminus Gang G Wang, Martina P Pasillas, and Mark P Kamps* Biomedical Sciences Graduate Program, University of California San Diego, School of Medicine, La Jolla, CA, USA Department of Pathology & Molecular Pathology Program, University of California San Diego, School of Medicine, La Jolla, CA, USA * Corresponding author; email: mkamps{at}ucsd.edu. Meis1 is a homeodomain transcription factor coexpressed with Hoxa9 in most human AML. In mouse models of leukemia produced by Hoxa9, Meis1 accelerates leukemogenesis. Because Hoxa9 immortalizes myeloid progenitors in the absence of Meis1 expression, the contribution of Meis1 towards leukemia remains unclear. Here, we describe a cultured progenitor model in which Meis1 programs leukemogenicity. Progenitors immortalized by Hoxa9 in culture are myeloid-lineage restricted and only infrequently caused leukemia after >250 days. Coexpressed Meis1 programmed rapid AML-initiating character, maintained multipotent progenitor potential, and induced expression of genes associated with short-term hematopoietic stem cells (HSC), such as FLT3 and CD34, whose expression also characterizes the leukemia-initiating stem cells of human AML. Meis1 leukemogenesis functions required binding to Pbx, binding to DNA, and a conserved function of its C-terminal tail. We hypothesize that Meis1 is required for the homing and survival of leukemic progenitors within their hematopoietic niches, functions mediated by HSC-specific genes such as CD34 and FLT3, respectively. This is the first example of a transcription factor oncoprotein (Meis1) that establishes expression of a tyrosine kinase oncoprotein (FLT3), and explains their coexpression in human leukemia. This cultured progenitor model will be useful to define the genetic basis of leukemogenesis involving Hoxa9 and Meis1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The HOX-MEIS connection in AML H. Jeffrey Lawrence and Corey Largman Blood 2005 106: 6-7. [Full Text] [PDF] This article has been cited by other articles: S.-L. Goh, Y. Looi, H. Shen, J. Fang, C. Bodner, M. Houle, A. C.-H. Ng, R. A. Screaton, and M. Featherstone Transcriptional Activation by MEIS1A in Response to Protein Kinase A Signaling Requires the Transducers of Regulated CREB Family of CREB Co-activators J. Biol. Chem., July 10, 2009; 284(28): 18904 - 18912. [Abstract] [Full Text] [PDF] S. R. Horman, C. S. Velu, A. Chaubey, T. Bourdeau, J. Zhu, W. E. 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[Abstract] [Full Text] [PDF] B. Dekel, S. Metsuyanim, K. M. Schmidt-Ott, E. Fridman, J. Jacob-Hirsch, A. Simon, J. Pinthus, Y. Mor, J. Barasch, N. Amariglio, et al. Multiple Imprinted and Stemness Genes Provide a Link between Normal and Tumor Progenitor Cells of the Developing Human Kidney. Cancer Res., June 15, 2006; 66(12): 6040 - 6049. [Abstract] [Full Text] [PDF] G. G. Wang, M. P. Pasillas, and M. P. Kamps Persistent Transactivation by Meis1 Replaces Hox Function in Myeloid Leukemogenesis Models: Evidence for Co-Occupancy of Meis1-Pbx and Hox-Pbx Complexes on Promoters of Leukemia-Associated Genes Mol. Cell. Biol., May 15, 2006; 26(10): 3902 - 3916. [Abstract] [Full Text] [PDF] J.-P. Bourquin, A. Subramanian, C. Langebrake, D. Reinhardt, O. Bernard, P. Ballerini, A. Baruchel, H. Cave, N. Dastugue, H. Hasle, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling PNAS, February 28, 2006; 103(9): 3339 - 3344. 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