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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2307-2314. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-04-1653. This Article Full Text (PDF) All Versions of this Article: 2004-04-1653v1 104/8/2307    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 Beslu, N. Articles by Sauvageau, G. Search for Related Content PubMed PubMed Citation Articles by Beslu, N. Articles by Sauvageau, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2004 Accepted June 7, 2004 Molecular Interactions Involved in HOXB4-Induced Activation of HSC Self-Renewal Nathalie Beslu, Jana Krosl, Melanie Laurin, Nadine Mayotte, R K Humphries, and Guy Sauvageau* Institut de Recherches en Immunologie et Cancer, Universite de Montreal, Montreal, Qc, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada Institut de Recherches en Immunologie et Cancer, Universite de Montreal, Montreal, Qc, Canada; Division of Hematology, Universite de Montreal, Montreal, Qc, Canada * Corresponding author; email: guy.sauvageau{at}umontreal.ca. HOXB4 overexpression induces unique in vivo and in vitro expansion of hemopoietic stem cells (HSCs) without causing leukemia. Very little is known about the molecular basis underlying HOXB4-induced HSC self-renewal. We now report the in vitro proliferation and in vivo expansion capacity of primary bone marrow (BM) cells engineered to overexpress selected HOXB4 point mutants lacking either the capacity to directly bind DNA (HOXB4(N51 A)), or to cooperate with members of the PBX family (HOXB4(WG)) in DNA-binding. The DNA-binding incompetent HOXB4 mutant failed to enhance the proliferation activity of transduced BM populations in vitro and HSC expansion in vivo. In contrast, the HOXB4(WG) mutant conferred a pronounced in vitro proliferation advantage to the transduced BM populations, and dramatically enhanced their in vivo regenerative potential. We also demonstrate a correlation between HOXB4 protein levels and in vitro proliferative capacity of primary BM cells. Our observations thus suggest that the capacity of HOXB4 to induce HSC expansions is DNA-binding dependent and does not require direct HOX/PBX interaction, and set the stage for identifying HOXB4-dependent targets involved in HSC expansion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Stem cell expansion: success and complexities Stefan Karlsson Blood 2004 104: 2210-2211. [Full Text] [PDF] This article has been cited by other articles: Z.-D. Gu, L.-Y. Shen, H. Wang, X.-M. Chen, Y. Li, T. Ning, and K.-N. Chen HOXA13 Promotes Cancer Cell Growth and Predicts Poor Survival of Patients with Esophageal Squamous Cell Carcinoma Cancer Res., June 15, 2009; 69(12): 4969 - 4973. [Abstract] [Full Text] [PDF] D. Metcalf, S. Glaser, S. Mifsud, L. Di Rago, and L. Robb The preleukemic state of mice reconstituted with Mixl1-transduced marrow cells PNAS, December 11, 2007; 104(50): 20013 - 20018. [Abstract] [Full Text] [PDF]

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