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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5163-5172. Prepublished online as a Blood First Edition Paper on March 13, 2008; DOI 10.1182/blood-2007-09-113654. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-113654v1 111/10/5163    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 Google Scholar Articles by Chen, J. Articles by Waldmann, T. A. PubMed PubMed Citation Articles by Chen, J. Articles by Waldmann, T. A. Related Collections Chemokines, Cytokines, and Interleukins Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism Jing Chen1, Mike Petrus1, Bonita R. Bryant1, Vinh Phuc Nguyen1, Mindy Stamer1, Carolyn K. Goldman1, Richard Bamford2, John C. Morris1, John E. Janik1, and Thomas A. Waldmann1 1 Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD; and 2 Transponics, Jacobus, PA The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-B motif in its proximal promoter, whereas IL-9 receptor- (IL-9R) expression is not induced by Tax. However, supporting a role for IL-9/IL-9R in ATL, a neutralizing monoclonal antibody directed toward IL-9R inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9R on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9R/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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