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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2673-2680
HEMATOPOIESIS
Forced expression of the Ikaros 6 isoform in human placental
blood CD34+ cells impairs their ability to differentiate
toward the B-lymphoid lineage
Cécile Tonnelle,
Florence Bardin,
Christine Maroc,
Anne-Marie Imbert,
Fanny Campa,
Ali Dalloul,
Christian Schmitt, and
Christian Chabannon
From the Institut Paoli-Calmettes, Centre
Régional de Lutte Contre le Cancer Provence-Alpes-Côte
d'Azur, Marseille, France; and Laboratoire d'Immunologie
Cellulaire, UMR7627 Centre National de la Recherche Scientifique,
Hôpital Pitié-Salpêtrière, Paris, France.
Studies in mice suggest that the Ikaros (Ik)
gene encodes several isoforms and is a critical regulator of
hematolymphoid differentiation. Little is known on the role of Ikaros
in human stem cell differentiation. Herein, the biological consequences
of the forced expression of Ikaros 6 (Ik6) in human placental blood
CD34+ progenitors are evaluated. Ik6 is one of the
isoforms produced from the Ikaros premessenger RNA by alternative
splicing and is thought to behave as a dominant negative isoform of the
gene product because it lacks the DNA binding domain present in
transcriptionally active isoforms. The results demonstrate that human
cord blood CD34+ cells that express high levels of Ik6 as a
result of retrovirally mediated gene transfer have a reduced capacity
to produce lymphoid B cells in 2 independent assays: (1) in vitro
reinitiation of human hematopoiesis during coculture with the MS-5
murine stromal cell line and (2) xenotransplantation in
nonobese diabetic-severe combined immunodeficient mice.
These results suggest that Ikaros plays an important role in stem cell
commitment in humans and that the balance between the different
isoforms is a key element of this regulatory system; they support the
hypothesis that posttranscriptional events can participate in the
control of human hematopoietic differentiation.

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