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 Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-05-1336.

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Blood, 15 March 2003, Vol. 101, No. 6, pp. 2219-2226

HEMATOPOIESIS

Ikaros regulates neutrophil differentiation

Alexis Dumortier, Peggy Kirstetter, Philippe Kastner, and Susan Chan

From the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National pour la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur (ULP), Illkirch Cedex, France.

The Ikaros gene encodes a zinc finger transcription factor that is selectively expressed by all hematopoietic cells. Although Ikaros is required for lymphocyte differentiation, its role in the myeloid lineage is unclear. We show here that Ikaros expression is temporally regulated during neutrophil differentiation: Ikaros is primarily expressed at immature stages and significantly less so in mature neutrophils. Furthermore IkL/L mice, harboring a hypomorphic mutation at the Ikaros locus, exhibit several defects during neutrophil differentiation. (1) IkL/L fetal livers contain high numbers of neutrophil lineage cells, and this increase is reflected in the number of GM-CSF-dependent progenitor cells. (2) The migratory potential and survival of neutrophil progenitors is altered in vitro. (3) Expression of the Gr-1 marker is delayed and repressed. In contrast, neutrophil function appears normal. These data demonstrate that Ikaros regulates early neutrophil differentiation but is dispensable in mature neutrophils.

© 2003 by The American Society of Hematology.
 

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