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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4917-4925. Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2005-10-4110. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4110v1 107/12/4917    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ye, D. Articles by Ilaria, R. L. Search for Related Content PubMed PubMed Citation Articles by Ye, D. Articles by Ilaria, R. L., Jr Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA STAT5 signaling is required for the efficient induction and maintenance of CML in mice Dan Ye, Nicholas Wolff, Li Li, Shumin Zhang, and Robert L. Ilaria, Jr From the Division of Hematology/Oncology, Department of Medicine; and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas. The role of signal transducers and activators of transcription 5 (STAT5) in chronic myelogenous leukemia (CML) is controversial. To clarify the role of STAT5 signaling in P210BCR/ABL leukemogenesis, P210 was introduced into primary murine STAT5A-deficient (STAT5A–/–) bone marrow (BM) cells, which, unlike STAT5A/5B double knockout BM cells, have no major intrinsic hematopoietic defects. Interestingly, only 21% of mice reconstituted with P210-transduced STAT5A–/– BM cells developed classic CML, compared with 80% to 100% of P210/STAT5A+/+ and P210/STAT5A+/–-reconstituted animals. The remainder of P210/STAT5A–/– animals died from an acute B-cell lymphoblastic leukemia (ALL)–like disease (32%) or a CML/ALL mix (47%), reflecting impairment in the induction and maintenance of CML, which normally predominates in this mouse model. Of mice that ultimately developed CML, P210/STAT5A–/– animals had prolonged survival and increased myeloid immaturity. Importantly, reconstitution of wild-type mice with BM cells coexpressing P210 and dominant-negative STAT5 also profoundly reduced the incidence of CML, without impairing the induction of ALL. Altogether, these findings indicate that STAT5 and STAT5A play an important role in the pathogenesis of the CML-like disease in mice. A greater understanding of the STAT5 target genes involved in CML induction may lead to new therapeutic targets that influence CML progenitor cell biology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. T. J. Wierenga, E. Vellenga, and J. J. Schuringa Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels Mol. Cell. Biol., November 1, 2008; 28(21): 6668 - 6680. [Abstract] [Full Text] [PDF] N. Harir, C. Boudot, K. Friedbichler, K. Sonneck, R. Kondo, S. Martin-Lanneree, L. Kenner, M. Kerenyi, S. Yahiaoui, V. Gouilleux-Gruart, et al. Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade Blood, September 15, 2008; 112(6): 2463 - 2473. [Abstract] [Full Text] [PDF] L. Hennighausen and G. W. 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Tomasson Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage Blood, May 1, 2007; 109(9): 3906 - 3914. [Abstract] [Full Text] [PDF] R. A. Van Etten Oncogenic signaling: new insights and controversies from chronic myeloid leukemia J. Exp. Med., March 19, 2007; 204(3): 461 - 465. [Abstract] [Full Text] [PDF] N. Harir, C. Pecquet, M. Kerenyi, K. Sonneck, B. Kovacic, R. Nyga, M. Brevet, I. Dhennin, V. Gouilleux-Gruart, H. Beug, et al. Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias Blood, February 15, 2007; 109(4): 1678 - 1686. [Abstract] [Full Text] [PDF] A. Rizo, E. Vellenga, G. de Haan, and J. J. Schuringa Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R210 - R219. [Abstract] [Full Text] [PDF]

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