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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4202-4209. Prepublished online as a Blood First Edition Paper on August 10, 2004; DOI 10.1182/blood-2003-10-3381. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3381v1 104/13/4202    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 Yee, K. W. H. Articles by Heinrich, M. C. Search for Related Content PubMed PubMed Citation Articles by Yee, K. W. H. Articles by Heinrich, M. C. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD–positive leukemic cells Kevin W. H. Yee, Marcus Schittenhelm, Anne-Marie O'Farrell, Ajia R. Town, Laura McGreevey, Troy Bainbridge, Julie M. Cherrington, and Michael C. Heinrich From the Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, OR; Clinic for Internal Medicine, Department of Hematology, Oncology, Immunology and Rheumatology, University of Tuebingen, Tuebingen, Germany; and Preclinical Research and Exploratory Development, SUGEN, South San Francisco, CA. Fetal liver tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutations are the most common molecular abnormality associated with adult acute myeloid leukemia (AML). To exploit this molecular target, a number of potent and specific FLT3 kinase inhibitors have been developed and are currently being tested in early phase clinical trials of patients with refractory AML. To explore the efficacy of combining a FLT3 inhibitor with standard AML chemotherapy drugs, we tested the effect of combining the FLT3 inhibitor SU11248 with cytarabine or daunorubicin on the proliferation and survival of cell lines expressing either mutant (FLT3 ITD or FLT3 D835V) or wild-type (WT) FLT3. SU11248 had additive-to-synergistic inhibitory effects on FLT3-dependent leukemic cell proliferation when combined with cytarabine or daunorubicin. The synergistic interaction of SU11248 and the traditional antileukemic agents was more pronounced for induction of apoptosis. SU11248 inhibited the proliferation of primary AML myeloblasts expressing mutant FLT3 ITD but not WT FLT3 protein. Combining SU11248 and cytarabine synergistically inhibited the proliferation of primary AML myeloblasts expressing FLT3 ITD but not WT FLT3 protein. These data suggest that the addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Shiotsu, H. Kiyoi, Y. Ishikawa, R. Tanizaki, M. Shimizu, H. Umehara, K. Ishii, Y. Mori, K. Ozeki, Y. Minami, et al. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation Blood, August 20, 2009; 114(8): 1607 - 1617. [Abstract] [Full Text] [PDF] A. Nordigarden, M. Kraft, P. Eliasson, V. Labi, E. W.-F. Lam, A. Villunger, and J.-I. 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