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Blood, 15 January 2007, Vol. 109, No. 2, pp. 500-502. Prepublished online as a Blood First Edition Paper on September 21, 2006; DOI 10.1182/blood-2006-05-025049. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-025049v1 109/2/500    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 Giles, F. J. Articles by Freedman, S. J. Search for Related Content PubMed PubMed Citation Articles by Giles, F. J. Articles by Freedman, S. J. Related Collections Brief Reports Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Brief report MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation Francis J. Giles1,, Jorge Cortes1, Dan Jones1, Donald Bergstrom2, Hagop Kantarjian1, and Steven J. Freedman2 1 Departments of Leukemia and Pathology, M. D. Anderson Cancer Center, Houston, TX; 2 Department of Clinical Oncology, Merck, Blue Bell, PA MK-0457 (VX-680) is a small-molecule aurora kinase (AK) inhibitor with preclinical antileukemia activity. The T315I BCR-ABL mutation mediates resistance to imatinib, nilotinib, and dasatinib. MK-0457 has in vitro activity against cells expressing wild-type or mutated BCR-ABL, including the T315I BCR-ABL mutation. Three patients with T315I abl-mutated chronic myeloid leukemia (CML) or Philadelphia chromosome (Ph)–positive acute lymphocytic leukemia (ALL) have achieved clinical responses to doses of MK-04547 that are not associated with adverse events. Higher MK-0457 dose levels were associated with clinical responses and down-regulation of CrkL phosphorylation in leukemia cells. The possible role of AK inhibition in these clinical responses requires further investigation. The currently reported cases are the first observed clinical activity of a kinase inhibitor against the T315I phenotype. The observation of responses in 3 patients with T315I phenotype–refractory CML or Ph-positive ALL, at doses of MK-0457 associated with no significant extramedullary toxicity, is very encouraging. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MK-0457: a light at the end of the tunnel? 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