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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1086-1096. Prepublished online as a Blood First Edition Paper on October 24, 2008; DOI 10.1182/blood-2008-01-132316. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-132316v1 113/5/1086    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 Kim, W.-I. Articles by Largaespada, D. A. Search for Related Content PubMed PubMed Citation Articles by Kim, W.-I. Articles by Largaespada, D. A. Related Collections Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia Won-Il Kim1,2, Ilze Matise2,3, Miechaleen D. Diers2, and David A. Largaespada1,2 1 Department of Genetics, Cell Biology, and Development and 2 Masonic Cancer Center, University of Minnesota, Minneapolis; and 3 Department of Veterinary Clinical Sciences, University of Minnesota, St Paul To study the oncogenic role of the NRAS oncogene (NRASG12V) in the context of acute myeloid leukemia (AML), we used a Vav promoter–tetracycline transactivator (Vav-tTA)–driven repressible TRE-NRASG12V transgene system in Mll-AF9 knock-in mice developing AML. Conditional repression of NRASG12V expression greatly reduced peripheral white blood cell (WBC) counts in leukemia recipient mice and induced apoptosis in the transplanted AML cells correlated with reduced Ras/Erk signaling. After marked decrease of AML blast cells, myeloproliferative disease (MPD)–like AML relapsed characterized by cells that did not express NRASG12V. In comparison with primary AML, the MPD-like AML showed significantly reduced aggressiveness, reduced myelosuppression, and a more differentiated phenotype. We conclude that, in AML induced by an Mll-AF9 transgene, NRASG12V expression contributes to acute leukemia maintenance by suppressing apoptosis and reducing differentiation of leukemia cells. Moreover, NRASG12V oncogene has a cell nonautonomous role in suppressing erythropoiesis that results in the MPD-like AML show significantly reduced ability to induce anemia. Our results imply that targeting NRAS or RAS oncogene-activated pathways is a good therapeutic strategy for AML and attenuating aggressiveness of relapsed AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. S. Collier, D. J. Adams, C. S. Hackett, L. E. Bendzick, K. Akagi, M. N. Davies, M. D. Diers, F. J. Rodriguez, A. M. Bender, C. Tieu, et al. Whole-Body Sleeping Beauty Mutagenesis Can Cause Penetrant Leukemia/Lymphoma and Rare High-Grade Glioma without Associated Embryonic Lethality Cancer Res., November 1, 2009; 69(21): 8429 - 8437. [Abstract] [Full Text] [PDF]

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