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Molecular and Cellular Biology, March 2005, p. 1645-1654, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1645-1654.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Ikaros Induces Quiescence and T-Cell Differentiation in a Leukemia Cell Line

Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Received 9 July 2004/ Returned for modification 30 August 2004/ Accepted 30 November 2004

Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that Ikaros has the characteristics of a tumor suppressor gene. In this report, we show that the introduction of Ikaros into an established mouse Ikaros null T leukemia cell line leads to growth arrest at the G₀/G₁ stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor p27^kip1, the induction of expression of T-cell differentiation markers, and a global and specific increase in histone H3 acetylation status. These studies provide strong evidence that Ikaros possesses the properties of a bona fide tumor suppressor gene for the T-cell lineage and offer insight into the mechanism of Ikaros's tumor suppressive activity.

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