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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-05-1550. This Article Full Text (PDF) All Versions of this Article: 2003-05-1550v1 102/8/2976    most recent Alert me when this article is cited Alert me if a correction is posted 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. Search for Related Content PubMed PubMed Citation Articles by Jiang, X. Articles by Eaves, C. Social Bookmarking                   What's this? Submitted May 15, 2003 Accepted June 5, 2003 Evidence for a positive role of SHIP in the BCR-ABL-mediated transformation of primitive murine hematopoietic cells and in human chronic myeloid leukemia Xiaoyan Jiang*, Matthew Stuible, Yves Chalandon, Andra Li, Wing Yiu Chan, Wolfgang Eisterer, Gerald Krystal, Allen Eaves, and Connie Eaves Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada * Corresponding author; email: xjiang{at}bccancer.bc.ca. Previous studies suggested that the SH2-containing inositol-5-phosphatase (SHIP) may play a tumor suppressor-like function in BCR-ABL-mediated leukemogenesis. To investigate this possibility, we first developed a new assay for quantitating transplantable multi-lineage leukemia-initiating cells (L-ICs) in hematopoietic stem cell (HSC)-enriched mouse bone marrow (BM) cells transduced with a BCR-ABL-GFP retrovirus. The frequency of L-ICs (1/430 Sca-1+lin- cells) was 7-fold lower than the frequency of HSCs in the Sca-1+lin- subset transduced with a control virus (1/65 cells). Forced BCR-ABL expression was also accompanied by a loss of normal HSC activity consistent with the acquisition of an increased probability of differentiation. Interestingly, the frequency and in vivo behavior of +/+ and SHIP-/- L-ICs were indistinguishable, and in vitro, Sca-1+lin- BCR-ABL-transduced SHIP-/- cells showed a modestly reduced factor-independence. Comparison of different populations of cells from chronic phase CML patients and normal human BM showed that the reduced expression of full-length SHIP proteins seen in the more mature (CD34-lin+) leukemic cells is not mirrored in the more primitive (CD34+lin-) leukemic cells. Thus SHIP expression appears to be differently altered in the early and late stages of differentiation of BCR-ABL-transformed cells underscoring the importance of the cellular context in which its mechanistic effects are analyzed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo Blood, February 15, 2006; 107(4): 1375 - 1382. [Abstract] [Full Text] [PDF] H. G. Jorgensen, M. Copland, E. K. Allan, X. 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