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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0220.

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Submitted January 25, 2002
Accepted March 29, 2002

Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells

R. K Humphries*, Christian Buske, Michaela Feuring-Buske, Carolina Abramovich, Karsten Spiekermann, Connie J Eaves, Laure Coulombel, Guy Sauvageau, and Donna E Hogge

Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Dept. of Medicine, University of British Columbia, Vancouver, BC, Canada
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; GSF-National Research Center for Environment and Health, and Dept. of Medicine III, Ludwigs-Maximilian University, Munich, Germany
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
GSF-National Research Center for Environment and Health, and Dept. of Medicine III, Ludwigs-Maximilian University, Munich, Germany
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Dept. of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
Faculte de Medecine, INSERM U421, Creteil, France
Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montreal, Montreal, QC, Canada

* Corresponding author; email: khumphri{at}bccancer.bc.ca.

Identification of the molecular mechanisms that can promote human hematopoietic stem cell amplification is a major goal in experimental and clinical hematology. Recent data indicate that a variety of regulatory molecules active in early development may also play a role in the maintenance of hematopoietic stem cells with repopulating activity. One important class of early developmental genes determining hematopoietic development are homeobox transcription factors. Here, we report that retrovirally-mediated expression of the homeobox gene HOXB4 rapidly triggers an increase in the number of human hematopoietic cord blood cells with stem cell and progenitor cell properties detected both by in vitro and in vivo assays. This growth enhancement extended across primitive myeloid-erythroid and B-lymphoid progenitors but did not lead to alterations in the balance of lympho-myeloid reconstitution in vivo suggesting that HOXB4 does not impact control of end-cell output. These findings reveal HOXB4 as a novel, positive regulator of the primitive growth activity of human hematopoietic progenitor cells and underline the relevance of early developmental factors for stem cell fate decisions.


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