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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-05-1324. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1324v1 100/10/3731    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 Jiang, X. Articles by Eaves, C. J. Search for Related Content PubMed PubMed Citation Articles by Jiang, X. Articles by Eaves, C. J. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2002, Vol. 100, No. 10, pp. 3731-3740 NEOPLASIA Primitive interleukin 3 null hematopoietic cells transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo Xiaoyan Jiang, Eddy Ng, Calvin Yip, Wolfgang Eisterer, Yves Chalandon, Matthew Stuible, Allen Eaves, and Connie J. Eaves From the Terry Fox Laboratory, British Columbia Cancer Agency, and the Departments of Medicine, Pathology, and Laboratory Medicine, and Medical Genetics, University of British Columbia, Vancouver, BC, Canada. Primitive chronic myeloid leukemia cells display a unique autocrine interleukin 3 (IL-3)/granulocyte-colony-stimluating factor (G-CSF) mechanism that may explain their abnormal proliferation and differentiation control. Here we show that BCR-ABL transduction of primitive Sca-1+ lin mouse bone marrow (BM) cells causes immediate activation of IL-3, G-CSF, and granulocyte macrophage-colony-stimulating factor (GM-CSF) expression in these cells. Their autocrine IL-3-mediated growth dependence is thus demonstrable only in clonal cultures where paracrine effects are reduced. Interestingly, upon continued culture, these cells produce large populations of rapidly proliferating mast cells in which only the IL-3 autocrine mechanism is consistently maintained, together with evidence of hyperphosphorylation of p210BCR-ABL and STAT5 and retention of a multilineage but attenuated in vivo leukemogenic potential characterized by a prolonged latency. BCR-ABL transduction of IL-3/ Sca-1+ lin BM cells initially activates GM-CSF and G-CSF production, factor independence, and the ability to generate phenotypically indistinguishable populations of mast cells. However, maintenance of factor independence, and p210BCR-ABL and STAT 5 activation beyond 4 to 6 weeks, requires rescue with an IL-3 transgene. The cultured BCR-ABL-transduced IL-3/ cells also lack leukemogenic activity in vivo. These findings provide new evidence that IL-3 production is a rapid, sustained, and biologically relevant consequence of BCR-ABL expression in primitive hematopoietic cells with multilineage leukemogenic activity. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. L. Zhou, Y. Zhao, A. Ringrose, D. DeGeer, E. Kennah, A. E.-J. Lin, G. Sheng, X.-J. Li, A. Turhan, and X. Jiang AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells J. Exp. Med., October 27, 2008; 205(11): 2657 - 2671. [Abstract] [Full Text] [PDF] X. Jiang, K. M. Saw, A. Eaves, and C. Eaves Instability of BCR-ABL Gene in Primary and Cultured Chronic Myeloid Leukemia Stem Cells J Natl Cancer Inst, May 2, 2007; 99(9): 680 - 693. [Abstract] [Full Text] [PDF] X. Jiang, Y. Zhao, W.-Y. Chan, S. Vercauteren, E. Pang, S. Kennedy, F. Nicolini, A. Eaves, and C. Eaves Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia Blood, May 15, 2004; 103(10): 3897 - 3904. [Abstract] [Full Text] [PDF] N. J. Donato, J. Y. Wu, J. Stapley, H. Lin, R. Arlinghaus, B. Aggarwal, S. Shishodin, M. Albitar, K. Hayes, H. Kantarjian, et al. Imatinib Mesylate Resistance Through BCR-ABL Independence in Chronic Myelogenous Leukemia Cancer Res., January 15, 2004; 64(2): 672 - 677. [Abstract] [Full Text] [PDF] X. Jiang, M. Stuible, Y. Chalandon, A. Li, W. Y. Chan, W. Eisterer, G. Krystal, A. Eaves, and C. Eaves Evidence for a positive role of SHIP in the BCR-ABL-mediated transformation of primitive murine hematopoietic cells and in human chronic myeloid leukemia Blood, October 15, 2003; 102(8): 2976 - 2984. [Abstract] [Full Text] [PDF] S. Wong, J. McLaughlin, D. Cheng, K. Shannon, L. Robb, and O. N. Witte IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease PNAS, September 30, 2003; 100(20): 11630 - 11635. [Abstract] [Full Text] [PDF]

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