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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1690-1697. Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2005-12-012773. This Article Full Text (PDF) All Versions of this Article: blood-2005-12-012773v1 108/5/1690    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 Wunderlich, M. Articles by Mulloy, J. C Search for Related Content PubMed PubMed Citation Articles by Wunderlich, M. Articles by Mulloy, J. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 10, 2005 Accepted April 24, 2006 Human CD34+ cells expressing the inv(16) fusion protein exhibit a myelomonocytic phenotype with greatly enhanced proliferative ability Mark Wunderlich, Ondrej Krejci, Junping Wei, and James C Mulloy* Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH, USA * Corresponding author; email: james.mulloy{at}cchmc.org. The t(16:16) and inv(16) are associated with FAB M4Eo myeloid leukemias and result in fusion of the CBFB gene to the MYH11 gene (encoding SMMHC). Knockout of CBFB causes embryonic lethality due to lack of definitive hematopoiesis. Although knockin of CBFB-MYH11 is not sufficient to cause disease, expression increases the incidence of leukemia when combined with cooperating events. While mouse models are valuable tools in the study of leukemogenesis, little is known about the contribution of CBF-SMMHC to human hematopoietic stem and progenitor cell self-renewal. We introduced the CBFB-MYH11 cDNA into human CD34+ cells via retroviral transduction. Transduced cells displayed an initial repression of progenitor activity but eventually dominated the culture, resulting in the proliferation of clonal populations for up to 7 months. Long-term cultures displayed a myelomonocytic morphology while retaining multi-lineage progenitor activity and engraftment in NOD/SCID-B2M-/- mice. Progenitor cells from long-term cultures showed altered expression of inv (16)-defining genes identified in microarray studies of human patient samples. This system will be useful in examining the effects of CBF-SMMHC on gene expression in the human pre-leukemic cell, in characterizing the effect of this oncogene on human stem cell biology and in defining its contribution to the development of leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Krejci, M. Wunderlich, H. Geiger, F.-S. Chou, D. Schleimer, M. Jansen, P. R. Andreassen, and J. C. Mulloy p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death Blood, February 15, 2008; 111(4): 2190 - 2199. [Abstract] [Full Text] [PDF]

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