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Blood, 22 October 2009, Vol. 114, No. 17, pp. 3629-3632. Prepublished online as a Blood First Edition Paper on August 26, 2009; DOI 10.1182/blood-2009-02-205146. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2009-02-205146v1 114/17/3629    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 Google Scholar Articles by Cutts, B. A. Articles by Bergo, M. O. PubMed PubMed Citation Articles by Cutts, B. A. Articles by Bergo, M. O. Related Collections Myeloid Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Brief report Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice Briony A. Cutts1,*, Anna-Karin M. Sjogren1,*, Karin M. E. Andersson1, Annika M. Wahlstrom1, Christin Karlsson1, Birgitta Swolin2, and Martin O. Bergo1 1 Wallenberg Laboratory, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg; and 2 Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase–activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS–induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RASG12D in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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