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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-11-3376. This Article Full Text (PDF) All Versions of this Article: 2002-11-3376v1 101/10/4088    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 Wong, S. Articles by Witte, O. Search for Related Content PubMed PubMed Citation Articles by Wong, S. Articles by Witte, O. Social Bookmarking                   What's this? Submitted November 7, 2002 Accepted January 2, 2003 Cell context specific effects of the BCR-ABL oncogene monitored in hematopoietic progenitors Stephane Wong, Jami McLaughlin, Donghui Cheng, and Owen Witte* Interdepartmental Ph.D. Program, Molecular Biology Institute, Los Angeles, CA, USA Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA Howard Hughes Medical Institute, Los Angeles, CA, USA * Corresponding author; email: owenw{at}microbio.ucla.edu. Acute BCR-ABL expression during in vitro hematopoietic development of embryonic stem (ES) cells causes expansion of multipotent and myeloid progenitors with a concomitant reduction in differentiation towards erythroblasts. Progenitor cell expansion is due to a rapid, cell autonomous, suppression of programmed cell death with an increase in expression of the anti-apoptotic molecule BCL-XL. Other anti-apoptotic effectors, including AKT, STAT5, and BCL-2 are not up regulated by BCR-ABL in this system. In addition, the pro-apoptotic P-38 MAPK pathway is suppressed by BCR-ABL expression in ES-derived hematopoietic progenitors. Inhibition of P-38 MAPK by the small molecule inhibitor SB203580 expanded ES-derived hematopoietic progenitors by an anti-apoptotic mechanism and is sufficient to expand ES-derived hematopoietic progenitors to levels approaching 80% of that seen following BCR-ABL expression. In the cellular context of ES-derived hematopoietic progenitors, BCR-ABL expression expands cells by suppressing programmed cell death with a set of anti-apoptotic pathways distinct from those previously reported in continuous cell line studies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Katsoulidis, A. Sassano, B. Majchrzak-Kita, N. Carayol, P. Yoon, A. Jordan, B. J. Druker, E. N. Fish, and L. C. 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