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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3007-3014. Prepublished online as a Blood First Edition Paper on November 28, 2006; DOI 10.1182/blood-2006-03-006718. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-006718v1 109/7/3007    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rimmelé, P. Articles by Guillouf, C. Search for Related Content PubMed PubMed Citation Articles by Rimmelé, P. Articles by Guillouf, C. Related Collections Hematopoiesis and Stem Cells Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation Pauline Rimmelé1, Olivier Kosmider1, Patrick Mayeux2, Françoise Moreau-Gachelin1, and Christel Guillouf1 1 Institut Curie, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 528, Paris, France; 2 Institut Cochin, Paris, France Overexpression of the transcription factor Spi-1/PU.1 in mice leads to acute erythroleukemia characterized by a differentiation block at the proerythroblastic stage. In this study, we made use of a new cellular system allowing us to reach graded expression of Spi-1 in preleukemic cells to dissect mechanisms of Spi-1/PU-1 in erythroleukemogenesis. This system is based on conditional production of 1 or 2 spi-1–interfering RNAs stably inserted into spi-1 transgenic proerythroblasts. We show that Spi-1 knock-down was sufficient to reinstate the erythroid differentiation program. This differentiation process was associated with an exit from the cell cycle. Evidence is provided that in the presence of erythropoietin (Epo), Spi-1 displays an antiapoptotic role that is independent of its function in blocking erythroid differentiation. Apoptosis inhibited by Spi-1 did not involve activation of the Fas/FasL signaling pathway nor a failure to activate Epo receptor (EpoR). Furthermore, we found that reducing the Spi-1 level yields to ERK dephosphorylation and increased phosphorylation of AKT and STAT5, suggesting that Spi-1 may affect major signaling pathways downstream of the EpoR in erythroid cells. These findings reveal 2 distinct roles for Spi-1 during erythroleukemogenesis: Spi-1 blocks the erythroid differentiation program and acts to impair apoptotic death in cooperation with an Epo signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020