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Blood, 1 January 2005, Vol. 105, No. 1, pp. 54-60. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-03-0891. This Article Full Text (PDF) All Versions of this Article: 2004-03-0891v1 105/1/54    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 Stone, R. M Articles by Griffin, J. D Search for Related Content PubMed PubMed Citation Articles by Stone, R. M Articles by Griffin, J. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2004 Accepted June 22, 2004 Acute myeloid leukemia patients with an activating mutation in FLT3 respond to a small molecule FLT3 tyrosine kinase inhibitor, PKC412 Richard M Stone*, Daniel J DeAngelo, Virginia Klimek, Ilene Galinsky, Eli Estey, Stephen D Nimer, Wilson Grandin, David Lebwohl, Yanfeng Wang, Pamela Cohen, Edward A Fox, Donna Neuberg, Jennifer Clark, D G Gilliland, and James D Griffin Dana-Farber Cancer Institute, Boston, MA, USA Memorial Sloan-Kettering Cancer Center, New York, NY, USA MD Anderson Cancer Center, Houston, TX, USA Novartis, Basil, Switzerland * Corresponding author; email: rstone{at}partners.org. Leukemic cells from 30% of patients with acute myeloid leukemia (AML) have an activating mutation in the FLT3 (fms-like tyrosine kinase) gene, which represents a target for drug therapy. We treated 20 patients, each with mutant FLT3 relapsed/refractory AML or high-grade myelodysplastic syndrome and not believed to be candidates for chemotherapy with a FLT3 tyrosine kinase inhibitor, PKC412 (N-benzoylstaurosporine), at a dose of 75 mg three times daily by mouth. The drug was generally well tolerated, although two patients developed fatal pulmonary events of unclear etiology. The peripheral blast count decreased by 50% in 14 patients (70%). Seven patients (35%) experienced a greater than 2-log reduction in peripheral blast count for at least 4 weeks (median response duration = 13 weeks, range 9-47 weeks); PKC412 reduced bone marrow blast counts by 50% in six patients (two of these to less than 5%). FLT3 autophosphorylation was inhibited in most of the responding patients, indicating in vivo target inhibition at the dose schedule used in this study. PKC412 is an oral tyrosine kinase inhibitor with clinical activity in patients with AML whose blasts have an activating mutation of FLT3, suggesting potential use in combination with active agents, such as chemotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Bornhauser, U. Oelschlaegel, U. Platzbecker, G. Bug, K. Lutterbeck, M. G. Kiehl, J. Schetelig, A. Kiani, T. Illmer, M. Schaich, et al. Monitoring of donor chimerism in sorted CD34+ peripheral blood cells allows the sensitive detection of imminent relapse after allogeneic stem cell transplantation Haematologica, November 1, 2009; 94(11): 1613 - 1617. [Abstract] [Full Text] [PDF] P. P. Zarrinkar, R. N. Gunawardane, M. D. Cramer, M. F. Gardner, D. Brigham, B. Belli, M. W. Karaman, K. W. Pratz, G. Pallares, Q. Chao, et al. 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