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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2880-2888. Prepublished online as a Blood First Edition Paper on July 13, 2007; DOI 10.1182/blood-2006-08-039073. This Article Full Text Full Text (PDF) Supplemental Protocols and Table All Versions of this Article: blood-2006-08-039073v1 110/8/2880    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 Schepers, H. Articles by Vellenga, E. Search for Related Content PubMed PubMed Citation Articles by Schepers, H. Articles by Vellenga, E. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Stem Cells in Hematology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells Hein Schepers1,2, Djoke van Gosliga1, Albertus T. J. Wierenga1, Bart J. L. Eggen2, Jan Jacob Schuringa1, and Edo Vellenga1 1 Division of Hematology, Department of Medicine, University Medical Center Groningen (UMCG), and 2 Department of Developmental Genetics, University of Groningen, Groningen, the Netherlands The transcription factor STAT5 fulfills a distinct role in the hematopoietic system, but its precise role in primitive human hematopoietic cells remains to be elucidated. Therefore, we performed STAT5 RNAi in sorted cord blood (CB) and acute myeloid leukemia (AML) CD34+ cells by lentiviral transduction and investigated effects of STAT5 downmodulation on the normal stem/progenitor cell compartment and the leukemic counterpart. STAT5 RNAi cells displayed growth impairment, without affecting their differentiation in CB and AML cultures on MS5 stroma. In CB, limiting-dilution assays demonstrated a 3.9-fold reduction in progenitor numbers. Stem cells were enumerated in long-term culture-initiating cell (LTC-IC) assays, and the average LTC-IC frequency was 3.25-fold reduced from 0.13% to 0.04% by STAT5 down-regulation. Single-cell sorting experiments of CB CD34+/CD38– cells demonstrated a 2-fold reduced cytokine-driven expansion, with a subsequent 2.3-fold reduction of progenitors. In sorted CD34+ AML cells with constitutive STAT5 phosphorylation (5/8), STAT5 RNAi demonstrated a reduction in cell number (72% ± 17%) and a decreased expansion (17 ± 15 vs 80 ± 58 in control cultures) at week 6 on MS5 stroma. Together, our data indicate that STAT5 expression is required for the maintenance and expansion of primitive hematopoietic stem and progenitor cells, both in normal as well as leukemic hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Reintroduction of C/EBP in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis Hein Schepers, Albertus T. J. Wierenga, Djoke van Gosliga, Bart J. L. Eggen, Edo Vellenga, and Jan Jacob Schuringa Blood 2007 110: 1317-1325. [Abstract] [Full Text] [PDF] This article has been cited by other articles: M. Heuser, L. M. Sly, B. Argiropoulos, F. Kuchenbauer, C. Lai, A. Weng, M. Leung, G. Lin, C. Brookes, S. Fung, et al. Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal Blood, November 5, 2009; 114(19): 3983 - 3993. [Abstract] [Full Text] [PDF] A. Rizo, S. Olthof, L. Han, E. Vellenga, G. de Haan, and J. J. Schuringa Repression of BMI1 in normal and leukemic human CD34+ cells impairs self-renewal and induces apoptosis Blood, August 20, 2009; 114(8): 1498 - 1505. [Abstract] [Full Text] [PDF] H. Nakajima, T. Tamura, M. Ito, F. Shibata, K. Kuroda, Y. Fukuchi, N. Watanabe, T. Kitamura, Y. Ikeda, and M. Handa SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription Blood, January 29, 2009; 113(5): 1027 - 1036. [Abstract] [Full Text] [PDF] 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] D. Kent, M. Copley, C. Benz, B. Dykstra, M. Bowie, and C. Eaves Regulation of Hematopoietic Stem Cells by the Steel Factor/KIT Signaling Pathway Clin. Cancer Res., April 1, 2008; 14(7): 1926 - 1930. [Abstract] [Full Text] [PDF] L. Hennighausen and G. W. Robinson Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B Genes & Dev., March 15, 2008; 22(6): 711 - 721. [Abstract] [Full Text] [PDF]

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