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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3337-3347. Prepublished online as a Blood First Edition Paper on January 23, 2009; DOI 10.1182/blood-2008-08-174813. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2008-08-174813v1 113/14/3337    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 Stankiewicz, M. J. Articles by Crispino, J. D. Search for Related Content PubMed PubMed Citation Articles by Stankiewicz, M. J. Articles by Crispino, J. D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 20, 2008 Accepted December 31, 2008 ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells Monika J. Stankiewicz and John D. Crispino* Division of Hematology/Oncology, Northwestern University, Chicago, IL, United States * Corresponding author; email: j-crispino{at}northwestern.edu. ETS2 and ERG are transcription factors, encoded on human chromosome 21 (Hsa21), that have been implicated in human cancer. Individuals with Down syndrome (DS), who are trisomic for Hsa21, are predisposed to Acute Megakaryoblastic Leukemia (AMKL). DS-AMKL blasts harbor a mutation in GATA1, which lead to loss of full-length protein but expression of the GATA-1s isoform. To assess the consequences of ETS protein mis-expression on megakaryopoiesis, we expressed ETS2, ERG and the related protein FLI1 in wild-type and Gata1-mutant murine fetal liver progenitors. These studies revealed that ETS2, ERG and FLI-1 facilitated the expansion of megakaryocytes from wild-type, Gata1-knockdown and Gata1s knock-in progenitors, but none of the genes could overcome the differentiation block characteristic of the Gata1-knockdown megakaryocytes. Furthermore, although overexpression of ETS proteins increased the proportion of CD41+ cells generated from Gata1s-knock-in progenitors, their expression led to a significant reduction in the more mature CD42 fraction. Serial replating assays revealed that overexpression of ERG or FLI1 immortalized Gata1-knockdown and Gata1s knock-in, but not wild-type, fetal liver progenitors. Immortalization was accompanied by activation of the JAK/STAT pathway, commonly seen in megakaryocytic malignancies. These findings provide evidence for synergy between alterations in GATA-1 and overexpression of ETS proteins in aberrant megakaryopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New GATA1 mutation in codon 2 leads to the earliest known premature stop codon in transient myeloproliferative disorder Sylvia Hoeller, Michel P. Bihl, Alexandar Tzankov, Thomas Kuehne, Christian Potthoff, and Elisabeth Bruder Blood 2009 114: 3717-3718. [Full Text] [PDF] This article has been cited by other articles: S. Hoeller, M. P. Bihl, A. Tzankov, T. Kuehne, C. Potthoff, and E. Bruder New GATA1 mutation in codon 2 leads to the earliest known premature stop codon in transient myeloproliferative disorder Blood, October 22, 2009; 114(17): 3717 - 3718. [Full Text] [PDF]

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