SEARCH:   Advanced

Blood, 15 June 2005, Vol. 105, No. 12, pp. 4792-4799. Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-11-4430. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4430v1 105/12/4792    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 Grundler, R. Articles by Duyster, J. Search for Related Content PubMed PubMed Citation Articles by Grundler, R. Articles by Duyster, J. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model Rebekka Grundler, Cornelius Miething, Christian Thiede, Christian Peschel, and Justus Duyster From the Department of Internal Medicine III, Technical University of Munich, Munich, Germany; and Med Klinik und Poliklinik I, Universtätsklinikum Carl Gustav Carus der Technischen Universität, Dresden, Germany. Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are the most common genetic alteration in acute myeloid leukemia (AML). Two distinct groups of FLT3 mutations are found: internal tandem duplications (ITDs) of the juxtamembrane region and point mutations within the tyrosine kinase domain (TKD). Recently, point mutations within the activation loop of FLT3 have also been described in childhood acute lymphoblastic leukemia (ALL). FLT3-ITD has been shown to induce a myeloproliferative syndrome in a murine bone marrow transplantation model. The phenotype of FLT3-TKD in mice has not yet been investigated. We transduced murine bone marrow with retrovirus-expressing FLT3-TKD mutants or FLT3-ITD and transplanted these cells into lethally irradiated mice. Mice that received a transplant of FLT3-ITD developed an oligoclonal myeloproliferative disease as previously described. In contrast, FLT3-TKD mutants induced an oligoclonal lymphoid disorder with longer latency and distinct hematologic manifestations: importantly, induction of the lymphoid phenotype was not due to a low number of transplanted cells. The lymphoid manifestation and longer latency of FLT3-TKD compared with FLT3-ITD mutants together with the lack of influence of FLT3-TKD mutations on the clinical outcome of patients with AML suggest differences in cell signaling between FLT3-TKD mutants and FLT3-ITDs. Indeed strong signal transducers and activators of transcription 5 (STAT5) activation could only be demonstrated for FLT3-ITDs. (Blood. 2005;105:4792-4799) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. P. Whitman, G. Marcucci, A. S. Ruppert, K. Mrozek, and C. D. Bloomfield Response: Conflicting data on the prognostic significance of FLT3-TKD mutations in cytogenetically normal acute myeloid leukemia (CN-AML) might be related to many factors, including techniques used to detect FLT3-TKD, differences in patient populations studied, and treatment regimens Blood, July 15, 2008; 112(2): 445 - 445. [Full Text] [PDF] L. Li, O. Piloto, H. B. Nguyen, K. Greenberg, K. Takamiya, F. Racke, D. Huso, and D. Small Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model Blood, April 1, 2008; 111(7): 3849 - 3858. [Abstract] [Full Text] [PDF] S. P. Whitman, A. S. Ruppert, M. D. Radmacher, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, F. Racke, B. L. Powell, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications Blood, February 1, 2008; 111(3): 1552 - 1559. [Abstract] [Full Text] [PDF] A. J. Mead, D. C. Linch, R. K. Hills, K. Wheatley, A. K. Burnett, and R. E. Gale FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia Blood, August 15, 2007; 110(4): 1262 - 1270. [Abstract] [Full Text] [PDF] C. Choudhary, C. Brandts, J. Schwable, L. Tickenbrock, B. Sargin, A. Ueker, F.-D. Bohmer, W. E. Berdel, C. Muller-Tidow, and H. Serve Activation mechanisms of STAT5 by oncogenic Flt3-ITD Blood, July 1, 2007; 110(1): 370 - 374. [Abstract] [Full Text] [PDF] K. Mrozek, G. Marcucci, P. Paschka, S. P. Whitman, and C. D. Bloomfield Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood, January 15, 2007; 109(2): 431 - 448. [Abstract] [Full Text] [PDF] H. Dohner Implication of the Molecular Characterization of Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 412 - 419. [Abstract] [Full Text] [PDF] D. J. DeAngelo, R. M. Stone, M. L. Heaney, S. D. Nimer, R. L. Paquette, R. B. Klisovic, M. A. Caligiuri, M. R. Cooper, J.-M. Lecerf, M. D. Karol, et al. Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics Blood, December 1, 2006; 108(12): 3674 - 3681. [Abstract] [Full Text] [PDF] S. Meshinchi, T. A. Alonzo, D. L. Stirewalt, M. Zwaan, M. Zimmerman, D. Reinhardt, G. J. L. Kaspers, N. A. Heerema, R. Gerbing, B. J. Lange, et al. Clinical implications of FLT3 mutations in pediatric AML Blood, December 1, 2006; 108(12): 3654 - 3661. [Abstract] [Full Text] [PDF] E. Heiss, K. Masson, C. Sundberg, M. Pedersen, J. Sun, S. Bengtsson, and L. Ronnstrand Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2 Blood, September 1, 2006; 108(5): 1542 - 1550. [Abstract] [Full Text] [PDF] J. L. Rocnik, R. Okabe, J.-C. Yu, B. H. Lee, N. Giese, D. P. Schenkein, and D. G. Gilliland Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD Blood, August 15, 2006; 108(4): 1339 - 1345. [Abstract] [Full Text] [PDF] L. Palmqvist, B. Argiropoulos, N. Pineault, C. Abramovich, L. M. Sly, G. Krystal, A. Wan, and R. K. Humphries The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia Blood, August 1, 2006; 108(3): 1030 - 1036. [Abstract] [Full Text] [PDF] C. Thiede, S. Koch, E. Creutzig, C. Steudel, T. Illmer, M. Schaich, G. Ehninger, and for the Deutsche Studieninitiative Leukamie (DSIL) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Blood, May 15, 2006; 107(10): 4011 - 4020. [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] C. Choudhary, J. Schwable, C. Brandts, L. Tickenbrock, B. Sargin, T. Kindler, T. Fischer, W. E. Berdel, C. Muller-Tidow, and H. Serve AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations Blood, July 1, 2005; 106(1): 265 - 273. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020