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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4469-4476. Prepublished online as a Blood First Edition Paper on September 15, 2009; DOI 10.1182/blood-2009-06-230169. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-06-230169v1 114/20/4469    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 Enzler, T. Articles by Kipps, T. J. PubMed PubMed Citation Articles by Enzler, T. Articles by Kipps, T. J. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Chronic lymphocytic leukemia of Eµ-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression Thomas Enzler13,*, Arnon P. Kater1,4,*, Weizhou Zhang2,*, George F. Widhopf, II1, Han-Yu Chuang1, Jason Lee1, Esther Avery1, Carlo M. Croce5, Michael Karin2, and Thomas J. Kipps1 1 Moores Cancer Center and 2 Laboratory of Gene Regulation and Signal Transduction, Departments of Medicine, Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla; 3 Department of Medicine, Stanford University School of Medicine, CA; 4 Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands; and 5 The Ohio State University Cancer Center, Columbus Results of heavy-water labeling studies have challenged the notion that chronic lymphocytic leukemia (CLL) represents an accumulation of noncycling B cells. We examined leukemia cell turnover in Eµ-TCL1 transgenic (TCL1-Tg) mice, which develop a CLL-like disease at 8 to 12 months of age. We found that leukemia cells in these mice not only had higher proportions of proliferating cells but also apoptotic cells than did nonleukemic lymphocytes. We crossed TCL1-Tg with BAFF-Tg mice, which express high levels of CD257. TCL1xBAFF-Tg mice developed CLL-like disease at a significantly younger age and had more rapid disease progression and shorter survival than TCL1-Tg mice. Leukemia cells of TCL1xBAFF-Tg mice had similar proportions of proliferating cells, but fewer proportions of dying cells, than did the CLL cells of TCL1-Tg mice. Moreover, leukemia cells from either TCL1xBAFF-Tg or TCL1-Tg mice produced more aggressive disease when transferred into BAFF-Tg mice than into wild-type (WT) mice. Neutralization of CD257 resulted in rapid reduction in circulating leukemia cells. These results indicate that the leukemia cells of TCL1-Tg mice undergo high levels of spontaneous apoptosis that is offset by relatively high rates of leukemia cell proliferation, which might allow for acquisition of mutations that contribute to disease evolution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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