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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1317-1325. Prepublished online as a Blood First Edition Paper on May 2, 2007; DOI 10.1182/blood-2006-10-052175. This Article Full Text Full Text (PDF) Erratum (v110,p2818) All Versions of this Article: blood-2006-10-052175v1 110/4/1317    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 Schuringa, J. J. Search for Related Content PubMed PubMed Citation Articles by Schepers, H. Articles by Schuringa, J. J. Related Collections Hematopoiesis and Stem Cells Neoplasia Gene Expression Stem Cells in Hematology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Reintroduction of C/EBP in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis Hein Schepers1,2, Albertus T. J. Wierenga1, Djoke van Gosliga1, Bart J. L. Eggen2, Edo Vellenga1, and Jan Jacob Schuringa1 1 Division of Hematology, Department of Medicine, University Medical Center Groningen, Groningen; 2 Department of Developmental Genetics, University of Groningen, Groningen, The Netherlands The CCAAT/enhancer binding protein (C/EBP) transcription factor is indispensable for myeloid differentiation. In various myeloid leukemias, C/EBP is mutated or functionally impaired due to decreased C/EBP expression or phosphorylation. In order to investigate the functional consequences of decreased C/EBP function in AML, we reintroduced C/EBP in primary CD34+ sorted acute myeloid leukemia (AML) cells using a lentiviral approach. Self-renewal and differentiation of primary AML stem cells were studied on long-term MS5 cocultures. Activation of C/EBP immediately led to a growth arrest in all AML cultures (N = 7), resulting in severely reduced expansion compared with control cultures. This growth arrest corresponded with enhanced myeloid differentiation as assessed by fluorescence-activated cell sorter (FACS) analysis for CD14, CD15, and CD11b. Myeloid differentiation was further confirmed by the up-regulation of neutrophil elastase and granulocyte colony-stimulating factor (G-CSF) receptor in C/EBP transduced cells. C/EBP-expressing AML CD34+ cells failed to generate second and third leukemic cobblestone areas (L-CAs) in serial replating experiments, while control cultures could be sequentially passaged for more than 4 times, indicating that reintroduction of C/EBP impaired the self-renewal capacity of the leukemic CD34+ compartment. Together, our data indicate that low C/EBP levels are necessary to maintain self-renewal and the immature character of AML stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells Hein Schepers, Djoke van Gosliga, Albertus T. J. Wierenga, Bart J. L. Eggen, Jan Jacob Schuringa, and Edo Vellenga Blood 2007 110: 2880-2888. [Abstract] [Full Text] [PDF] This article has been cited by other articles: H. Schepers, D. van Gosliga, A. T. J. Wierenga, B. J. L. Eggen, J. J. Schuringa, and E. Vellenga STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells Blood, October 15, 2007; 110(8): 2880 - 2888. [Abstract] [Full Text] [PDF]

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