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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2952-2954. Prepublished online as a Blood First Edition Paper on December 7, 2004; DOI 10.1182/blood-2004-07-2758. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2758v1 105/7/2952    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 Walters, D. K. Articles by Druker, B. J. Search for Related Content PubMed PubMed Citation Articles by Walters, D. K. Articles by Druker, B. J. Related Collections Oncogenes and Tumor Suppressors Brief Reports Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518 Denise K. Walters, Eric P. Stoffregen, Michael C. Heinrich, Michael W. Deininger, and Brian J. Druker From the Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, and Portland Veterans Affairs (VA) Medical Center, Portland, OR. FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is constitutively activated in approximately 30% of acute myelogenous leukemia (AML) patients and appears to confer an adverse prognosis. Thus, development of inhibitors and/or antibodies that specifically target FLT3 has been of substantial interest. In this regard, phase 1 and 2 trials involving FLT3 inhibitors have recently reported FLT3 inhibition and leukemic blast reduction in some patients. Despite this, issues such as specificity and resistance need to be addressed. Consequently, the development of alternative approaches for targeting FLT3 would be of great consequence. In the present report, we demonstrate that FLT3 siRNA effectively down-regulates FLT3 expression in Ba/F3 cells transfected with FLT3 containing an activating internal tandem duplication (ITD) in the juxtamembrane domain and FLT3-ITD–positive Molm-14 human leukemia cells. Treatment with the FLT3 siRNA results in growth inhibition and apoptosis of these cells. Furthermore, siRNA-induced down-regulation of FLT3 increased the sensitivity of both cell lines to treatment with the FLT3 inhibitor MLN518. This illustrates the potential benefit of combined therapeutic approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: How to interfere with FLT3 Martin Sattler Blood 2005 105: 2625-2626. [Full Text] [PDF] This article has been cited by other articles: C. Walz, B. J. Crowley, H. E. Hudon, J. L. Gramlich, D. S. Neuberg, K. Podar, J. D. Griffin, and M. Sattler Activated Jak2 with the V617F Point Mutation Promotes G1/S Phase Transition J. Biol. Chem., June 30, 2006; 281(26): 18177 - 18183. [Abstract] [Full Text] [PDF] F. Heidel, F. K. Solem, F. Breitenbuecher, D. B. Lipka, S. Kasper, M. H. Thiede, C. Brandts, H. Serve, J. Roesel, F. Giles, et al. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain Blood, January 1, 2006; 107(1): 293 - 300. [Abstract] [Full Text] [PDF]

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