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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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Blood, 1 August 2002, Vol. 100, No. 3, pp. 862-868
HEMATOPOIESIS
Deregulated expression of HOXB4 enhances the primitive growth
activity of human hematopoietic cells
Christian Buske,
Michaela Feuring-Buske,
Carolina Abramovich,
Karsten Spiekermann,
Connie J. Eaves,
Laure Coulombel,
Guy Sauvageau,
Donna E. Hogge, and
R. Keith Humphries
From the Terry Fox Laboratory, British Columbia Cancer
Agency, and the Department of Medical Genetics and Department of
Medicine, University of British Columbia, Vancouver, British Columbia,
Canada; the GSF-National Research Center for Environment and Health,
and Department of Medicine III, Grosshadern, Ludwigs-Maximilian
University Munich, Munich, Germany; INSERM U421, Faculté de
Médecine, Créteil, France; and Laboratory of Molecular
Genetics of Hemopoietic Stem Cells, Clinical Research Institute of
Montreal, Montreal, Quebec, Canada.
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
lymphomyeloid reconstitution in vivo, suggesting that HOXB4
does not affect 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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