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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4261-4268. Prepublished online as a Blood First Edition Paper on September 8, 2005; DOI 10.1182/blood-2004-11-4468. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4468v1 106/13/4261    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 Xu, Q. Articles by Carroll, M. Search for Related Content PubMed PubMed Citation Articles by Xu, Q. Articles by Carroll, M. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA mTOR regulates cell survival after etoposide treatment in primary AML cells Qing Xu, James E. Thompson, and Martin Carroll From the Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA. Acute myeloid leukemia cells have constitutive activation of phosphatidylinositol 3(PI3) kinase and require PI3 kinase activation for survival; however, the function of the PI3 kinase pathway in the survival of leukemic cells is poorly defined. We have studied the role of one PI3 kinase substrate, mTOR (mammalian target of rapamycin), in primary leukemic cells. In initial experiments, we have defined a novel growth medium that improves survival of acute myeloid leukemia (AML) blasts in long-term suspension culture and the survival of leukemic stem cells in short-term cultures. Inhibition of mTOR using rapamycin leads to a modest decrease in cell survival after 2 days of incubation with more significant decrease in survival after 7 days of culture. However, when rapamycin is added to etoposide in 2-day cultures, there is a dramatic increase in the cytotoxicity of etoposide against AML blasts. Furthermore, etoposide consistently decreased the engraftment of AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals, and this effect was enhanced by coincubation with rapamycin, demonstrating that mTOR regulates survival of AML stem cells after etoposide treatment. These results suggest that rapamycin in combination with etoposide-based chemotherapy may be efficacious in the treatment of AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. E. Perl, M. T. Kasner, D. E. Tsai, D. T. Vogl, A. W. Loren, S. J. Schuster, D. L. Porter, E. A. Stadtmauer, S. C. 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