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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2190-2197. Prepublished online as a Blood First Edition Paper on November 16, 2006; DOI 10.1182/blood-2005-01-031930. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-01-031930v1 109/5/2190    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, Z. Articles by Klug, C. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, Z. Articles by Klug, C. A. Related Collections Gene Expression Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Expression of a non–DNA-binding isoform of Helios induces T-cell lymphoma in mice Zheng Zhang1, C. Scott Swindle1, John T. Bates1, Rose Ko2, Claudiu V. Cotta3, and Christopher A. Klug1,3 1 Departments of Microbiology, 2 Biochemistry, and 3 Pathology, Division of Developmental and Clinical Immunology, University of Alabama at Birmingham Helios is a zinc-finger protein belonging to the Ikaros family of transcriptional regulators. It is expressed, along with Ikaros, throughout early stages of thymocyte development where it quantitatively associates with Ikaros through C-terminal zinc-finger domains that mediate heterodimerization between Ikaros family members. To understand the role of Helios in T-cell development, we used a retroviral vector to express full-length Helios or a Helios isoform that lacked the N-terminal DNA-binding domain in hematopoietic progenitor cells of reconstituted mice. Constitutive expression of full-length Helios resulted in an inhibition of T-cell development at the double-negative stage within the thymus. Although expression of the DNA-binding mutant of Helios did not contribute to developmental abnormalities at early times after transplantation, 60% of animals that expressed the Helios DNA-binding mutant developed an aggressive and transplantable T-cell lymphoma 4 to 10 months after transplantation. These results demonstrate a vital function for Helios in maintaining normal homeostasis of developing T cells and formally show that non–DNA-binding isoforms of Helios are lymphomagenic if aberrantly expressed within the T-cell lineage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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