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Related Collections Hematopoiesis and Stem Cells Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2000, Vol. 96, No. 12, pp. 3907-3914 NEOPLASIA Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways Masao Mizuki, Regina Fenski, Hartmut Halfter, Itaru Matsumura, Rainer Schmidt, Carsten Müller, Wolfram Grüning, Karsten Kratz-Albers, Susanne Serve, Claudia Steur, Thomas Büchner, Joachim Kienast, Yuzuru Kanakura, Wolfgang E. Berdel, and Hubert Serve From the Department of Medicine/Hematology and Oncology, and the Department of Neurology, University of Münster, Germany and the Department of Hematology and Oncology, Osaka University Medical School, Japan. Somatic mutations of the receptor tyrosine kinase Flt3 consisting of internal tandem duplications (ITD) occur in 20% of patients with acute myeloid leukemia. They are associated with a poor prognosis of the disease. In this study, we characterized the oncogenic potential and signaling properties of Flt3 mutations. We constructed chimeric molecules that consisted of the murine Flt3 backbone and a 510-base pair human Flt3 fragment, which contained either 4 different ITD mutants or the wild-type coding sequence. Flt3 isoforms containing ITD mutations (Flt3-ITD) induced factor-independent growth and resistance to radiation-induced apoptosis in 32D cells. Cells containing Flt3-ITD, but not those containing wild-type Flt3 (Flt3-WT), formed colonies in methylcellulose. Injection of 32D/Flt3-ITD induced rapid development of a leukemia-type disease in syngeneic mice. Flt3-ITD mutations exhibited constitutive autophosphorylation of the immature form of the Flt3 receptor. Analysis of the involved signal transduction pathways revealed that Flt3-ITD only slightly activated the MAP kinases Erk1 and 2 and the protein kinase B (Akt) in the absence of ligand and retained ligand-induced activation of these enzymes. However, Flt3-ITD led to strong factor-independent activation of STAT5. The relative importance of the STAT5 and Ras pathways for ITD-induced colony formation was assessed by transfection of dominant negative (dn) forms of these proteins: transfection of dnSTAT5 inhibited colony formation by 50%. Despite its weak constitutive activation by Flt3-ITD, dnRas also strongly inhibited Flt3-ITD-mediated colony formation. Taken together, Flt3-ITD mutations induce factor-independent growth and leukemogenesis of 32D cells that are mediated by the Ras and STAT5 pathways. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. 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Fischer Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor Blood, April 23, 2009; 113(17): 4074 - 4077. [Abstract] [Full Text] [PDF] D. Schmidt-Arras, S.-A. Bohmer, S. Koch, J. P. Muller, L. Blei, H. Cornils, R. Bauer, S. Korasikha, C. Thiede, and F.-D. Bohmer Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality Blood, April 9, 2009; 113(15): 3568 - 3576. [Abstract] [Full Text] [PDF] N. von Bubnoff, R. A. Engh, E. Aberg, J. Sanger, C. Peschel, and J. Duyster FMS-Like Tyrosine Kinase 3-Internal Tandem Duplication Tyrosine Kinase Inhibitors Display a Nonoverlapping Profile of Resistance Mutations In vitro Cancer Res., April 1, 2009; 69(7): 3032 - 3041. [Abstract] [Full Text] [PDF] C. Reindl, H. Quentmeier, K. Petropoulos, P. A. Greif, T. Benthaus, B. Argiropoulos, G. Mellert, S. Vempati, J. Duyster, C. Buske, et al. CBL Exon 8/9 Mutants Activate the FLT3 Pathway and Cluster in Core Binding Factor/11q Deletion Acute Myeloid Leukemia/Myelodysplastic Syndrome Subtypes Clin. Cancer Res., April 1, 2009; 15(7): 2238 - 2247. [Abstract] [Full Text] [PDF] A. Nordigarden, M. Kraft, P. Eliasson, V. Labi, E. W.-F. Lam, A. Villunger, and J.-I. Jonsson BH3-only protein Bim more critical than Puma in tyrosine kinase inhibitor-induced apoptosis of human leukemic cells and transduced hematopoietic progenitors carrying oncogenic FLT3 Blood, March 5, 2009; 113(10): 2302 - 2311. [Abstract] [Full Text] [PDF] N. Harir, C. Boudot, K. Friedbichler, K. Sonneck, R. Kondo, S. Martin-Lanneree, L. Kenner, M. Kerenyi, S. Yahiaoui, V. Gouilleux-Gruart, et al. Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade Blood, September 15, 2008; 112(6): 2463 - 2473. [Abstract] [Full Text] [PDF] S. Vempati, C. Reindl, U. Wolf, R. Kern, K. Petropoulos, V. M. Naidu, C. Buske, W. Hiddemann, T. M. Kohl, and K. Spiekermann Transformation by Oncogenic Mutants and Ligand-Dependent Activation of FLT3 Wild-type Requires the Tyrosine Residues 589 and 591 Clin. Cancer Res., July 15, 2008; 14(14): 4437 - 4445. [Abstract] [Full Text] [PDF] B. Basham, M. Sathe, J. Grein, T. McClanahan, A. D'Andrea, E. Lees, and A. Rascle In vivo identification of novel STAT5 target genes Nucleic Acids Res., June 1, 2008; 36(11): 3802 - 3818. [Abstract] [Full Text] [PDF] C. Nishioka, T. Ikezoe, J. Yang, A. Miwa, T. Tasaka, Y. Kuwayama, K. Togitani, H. P. Koeffler, and A. Yokoyama Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo Blood, May 15, 2008; 111(10): 5086 - 5092. [Abstract] [Full Text] [PDF] L. Bullinger, K. Dohner, R. Kranz, C. Stirner, S. Frohling, C. Scholl, Y. H. Kim, R. F. Schlenk, R. Tibshirani, H. Dohner, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML Blood, May 1, 2008; 111(9): 4490 - 4495. [Abstract] [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] R. E. Gale, C. Green, C. Allen, A. J. Mead, A. K. Burnett, R. K. Hills, D. C. Linch, and on behalf of the Medical Research Council Adult Le The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia Blood, March 1, 2008; 111(5): 2776 - 2784. [Abstract] [Full Text] [PDF] U. Bacher, C. Haferlach, W. Kern, T. Haferlach, and S. Schnittger Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients Blood, March 1, 2008; 111(5): 2527 - 2537. [Abstract] [Full Text] [PDF] E. V. Barry, J. J. Clark, J. Cools, J. Roesel, and D. G. Gilliland Uniform sensitivity of FLT3 activation loop mutants to the tyrosine kinase inhibitor midostaurin Blood, December 15, 2007; 110(13): 4476 - 4479. [Abstract] [Full Text] [PDF] B. Sargin, C. Choudhary, N. Crosetto, M. H. H. Schmidt, R. Grundler, M. Rensinghoff, C. Thiessen, L. Tickenbrock, J. Schwable, C. Brandts, et al. Flt3-dependent transformation by inactivating c-Cbl mutations in AML Blood, August 1, 2007; 110(3): 1004 - 1012. [Abstract] [Full Text] [PDF] S. Vempati, C. Reindl, S. K. Kaza, R. Kern, T. Malamoussi, M. Dugas, G. Mellert, S. Schnittger, W. Hiddemann, and K. Spiekermann Arginine 595 is duplicated in patients with acute leukemias carrying internal tandem duplications of FLT3 and modulates its transforming potential Blood, July 15, 2007; 110(2): 686 - 694. [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] L. Pearn, J. Fisher, A. K. Burnett, and R. L. Darley The role of PKC and PDK1 in monocyte lineage specification by Ras Blood, May 15, 2007; 109(10): 4461 - 4469. [Abstract] [Full Text] [PDF] Y. Dai, P. Khanna, S. Chen, X.-Y. Pei, P. Dent, and S. Grant Statins synergistically potentiate 7-hydroxystaurosporine (UCN-01) lethality in human leukemia and myeloma cells by disrupting Ras farnesylation and activation Blood, May 15, 2007; 109(10): 4415 - 4423. [Abstract] [Full Text] [PDF] S. Agrawal, W.-K. Hofmann, N. Tidow, M. Ehrich, D. v. d. Boom, S. Koschmieder, W. E. Berdel, H. Serve, and C. Muller-Tidow The C/EBP{delta} tumor suppressor is silenced by hypermethylation in acute myeloid leukemia Blood, May 1, 2007; 109(9): 3895 - 3905. [Abstract] [Full Text] [PDF] N. Harir, C. Pecquet, M. Kerenyi, K. Sonneck, B. Kovacic, R. Nyga, M. Brevet, I. Dhennin, V. Gouilleux-Gruart, H. Beug, et al. Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias Blood, February 15, 2007; 109(4): 1678 - 1686. [Abstract] [Full Text] [PDF] M. M. Stanford, J. W. Barrett, S. H. Nazarian, S. Werden, and G. McFadden Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells J. Virol., February 1, 2007; 81(3): 1251 - 1260. [Abstract] [Full Text] [PDF] T. Kawashima, Y. C. Bao, Y. Nomura, Y. Moon, Y. Tonozuka, Y. Minoshima, T. Hatori, A. Tsuchiya, M. Kiyono, T. Nosaka, et al. Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors J. Cell Biol., December 18, 2006; 175(6): 937 - 946. [Abstract] [Full Text] [PDF] E. Kulimova, E. Oelmann, G. Bisping, J. Kienast, R. M. Mesters, J. Schwable, F. Hilberg, G. J. Roth, G. Munzert, M. Stefanic, et al. Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors Mol. Cancer Ther., December 1, 2006; 5(12): 3105 - 3112. [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 (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1435 - 1435. [Abstract] [PDF] S. Corbacioglu, M. Kilic, M.-A. Westhoff, D. Reinhardt, S. Fulda, and K.-M. Debatin Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin Blood, November 15, 2006; 108(10): 3504 - 3513. [Abstract] [Full Text] [PDF] T. Ikezoe, C. Nishioka, T. Tasaka, Y. Yang, N. Komatsu, K. Togitani, H. P. Koeffler, and H. Taguchi The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling. Mol. Cancer Ther., October 1, 2006; 5(10): 2522 - 2530. [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] N. Omidvar, L. Pearn, A. K. Burnett, and R. L. Darley Ral Is both Necessary and Sufficient for the Inhibition of Myeloid Differentiation Mediated by Ras Mol. Cell. Biol., May 15, 2006; 26(10): 3966 - 3975. [Abstract] [Full Text] [PDF] D. L. Stirewalt, K. J. Kopecky, S. Meshinchi, J. H. Engel, E. L. Pogosova-Agadjanyan, J. Linsley, M. L. Slovak, C. L. Willman, and J. P. Radich Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia Blood, May 1, 2006; 107(9): 3724 - 3726. [Abstract] [Full Text] [PDF] C. Reindl, K. Bagrintseva, S. Vempati, S. Schnittger, J. W. Ellwart, K. Wenig, K.-P. Hopfner, W. Hiddemann, and K. Spiekermann Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML Blood, May 1, 2006; 107(9): 3700 - 3707. [Abstract] [Full Text] [PDF] Z. Zeng, I. J. Samudio, W. Zhang, Z. Estrov, H. Pelicano, D. Harris, O. Frolova, N. Hail Jr., W. Chen, S. M. Kornblau, et al. Simultaneous Inhibition of PDK1/AKT and Fms-Like Tyrosine Kinase 3 Signaling by a Small-Molecule KP372-1 Induces Mitochondrial Dysfunction and Apoptosis in Acute Myelogenous Leukemia. Cancer Res., April 1, 2006; 66(7): 3737 - 3746. [Abstract] [Full Text] [PDF] H. S. Radomska, D. S. Basseres, R. Zheng, P. Zhang, T. Dayaram, Y. Yamamoto, D. W. Sternberg, N. Lokker, N. A. Giese, S. K. Bohlander, et al. Block of C/EBP{alpha} function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations J. Exp. Med., February 21, 2006; 203(2): 371 - 381. [Abstract] [Full Text] [PDF] H. Liu, Y. Qiu, L. Xiao, and F. Dong Involvement of Protein Kinase C{epsilon} in the Negative Regulation of Akt Activation Stimulated by Granulocyte Colony-Stimulating Factor J. Immunol., February 15, 2006; 176(4): 2407 - 2413. [Abstract] [Full Text] [PDF] D. Small FLT3 Mutations: Biology and Treatment Hematology, January 1, 2006; 2006(1): 178 - 184. [Abstract] [Full Text] [PDF] B. F. Goemans, C. M. Zwaan, A. Harlow, A. H. Loonen, B. E. S. Gibson, K. Hahlen, D. Reinhardt, U. Creutzig, M. C. Heinrich, and G. J. L. Kaspers In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets Blood, November 15, 2005; 106(10): 3532 - 3537. [Abstract] [Full Text] [PDF] C. H. Brandts, B. Sargin, M. Rode, C. Biermann, B. Lindtner, J. Schwable, H. Buerger, C. Muller-Tidow, C. Choudhary, M. McMahon, et al. Constitutive Activation of Akt by Flt3 Internal Tandem Duplications Is Necessary for Increased Survival, Proliferation, and Myeloid Transformation Cancer Res., November 1, 2005; 65(21): 9643 - 9650. [Abstract] [Full Text] [PDF] D. Zhuang, Y. Qiu, S. J. Haque, and F. Dong Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1 J. Leukoc. Biol., October 1, 2005; 78(4): 1008 - 1015. [Abstract] [Full Text] [PDF] X. Yang, L. Liu, D. Sternberg, L. Tang, I. Galinsky, D. DeAngelo, and R. Stone The FLT3 Internal Tandem Duplication Mutation Prevents Apoptosis in Interleukin-3-Deprived BaF3 Cells Due to Protein Kinase A and Ribosomal S6 Kinase 1-Mediated BAD Phosphorylation at Serine 112 Cancer Res., August 15, 2005; 65(16): 7338 - 7347. [Abstract] [Full Text] [PDF] M. Levis, K. M. Murphy, R. Pham, K.-T. Kim, A. Stine, L. Li, I. McNiece, B. D. Smith, and D. Small Internal tandem duplications of the FLT3 gene are present in leukemia stem cells Blood, July 15, 2005; 106(2): 673 - 680. [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] R. Grundler, C. Miething, C. Thiede, C. Peschel, and J. Duyster FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model Blood, June 15, 2005; 105(12): 4792 - 4799. [Abstract] [Full Text] [PDF] D.-E. Schmidt-Arras, A. Bohmer, B. Markova, C. Choudhary, H. Serve, and F.-D. Bohmer Tyrosine Phosphorylation Regulates Maturation of Receptor Tyrosine Kinases Mol. Cell. Biol., May 1, 2005; 25(9): 3690 - 3703. [Abstract] [Full Text] [PDF] T. Illmer, C. Thiede, A. Fredersdorf, S. Stadler, A. Neubauer, G. Ehninger, and M. Schaich Activation of the RAS Pathway Is Predictive for a Chemosensitive Phenotype of Acute Myelogenous Leukemia Blasts Clin. Cancer Res., May 1, 2005; 11(9): 3217 - 3224. [Abstract] [Full Text] [PDF] K. Bagrintseva, S. Geisenhof, R. Kern, S. Eichenlaub, C. Reindl, J. W. Ellwart, W. Hiddemann, and K. Spiekermann FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L) Blood, May 1, 2005; 105(9): 3679 - 3685. [Abstract] [Full Text] [PDF] L. Tickenbrock, J. Schwable, M. Wiedehage, B. Steffen, B. Sargin, C. Choudhary, C. Brandts, W. E. Berdel, C. Muller-Tidow, and H. Serve Flt3 tandem duplication mutations cooperate with Wnt signaling in leukemic signal transduction Blood, May 1, 2005; 105(9): 3699 - 3706. [Abstract] [Full Text] [PDF] S. Fukuda, H. E. Broxmeyer, and L. M. Pelus Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1{alpha}(CXCL12)/CXCR4 axis Blood, April 15, 2005; 105(8): 3117 - 3126. [Abstract] [Full Text] [PDF] J. Schwable, C. Choudhary, C. Thiede, L. Tickenbrock, B. Sargin, C. Steur, M. Rehage, A. Rudat, C. Brandts, W. E. Berdel, et al. RGS2 is an important target gene of Flt3-ITD mutations in AML and functions in myeloid differentiation and leukemic transformation Blood, March 1, 2005; 105(5): 2107 - 2114. [Abstract] [Full Text] [PDF] P. Chen, M. Levis, P. Brown, K.-T. Kim, J. Allebach, and D. Small FLT3/ITD Mutation Signaling Includes Suppression of SHP-1 J. Biol. Chem., February 18, 2005; 280(7): 5361 - 5369. [Abstract] [Full Text] [PDF] K.-T. Kim, K. Baird, J.-Y. Ahn, P. Meltzer, M. Lilly, M. Levis, and D. Small Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival Blood, February 15, 2005; 105(4): 1759 - 1767. [Abstract] [Full Text] [PDF] W. Fiedler, H. Serve, H. Dohner, M. Schwittay, O. G. Ottmann, A.-M. O'Farrell, C. L. Bello, R. Allred, W. C. Manning, J. M. Cherrington, et al. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease Blood, February 1, 2005; 105(3): 986 - 993. [Abstract] [Full Text] [PDF] P. Brown, M. Levis, S. Shurtleff, D. Campana, J. Downing, and D. Small FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression Blood, January 15, 2005; 105(2): 812 - 820. [Abstract] [Full Text] [PDF] M. Wadleigh, D. J. DeAngelo, J. D. Griffin, and R. M. Stone After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies Blood, January 1, 2005; 105(1): 22 - 30. [Abstract] [Full Text] [PDF] K. Y. Chung, G. Morrone, J. J. Schuringa, B. Wong, D. C. Dorn, and M. A. S. Moore Enforced expression of an Flt3 internal tandem duplication in human CD34+ cells confers properties of self-renewal and enhanced erythropoiesis Blood, January 1, 2005; 105(1): 77 - 84. [Abstract] [Full Text] [PDF] T. Kindler, F. Breitenbuecher, S. Kasper, E. Estey, F. Giles, E. Feldman, G. Ehninger, G. Schiller, V. Klimek, S. D. Nimer, et al. Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML) Blood, January 1, 2005; 105(1): 335 - 340. [Abstract] [Full Text] [PDF] K. W. H. Yee, M. Schittenhelm, A.-M. O'Farrell, A. R. Town, L. McGreevey, T. Bainbridge, J. M. Cherrington, and M. C. Heinrich Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells Blood, December 15, 2004; 104(13): 4202 - 4209. [Abstract] [Full Text] [PDF] N. J. Lacayo, S. Meshinchi, P. Kinnunen, R. Yu, Y. Wang, C. M. Stuber, L. Douglas, R. Wahab, D. L. Becton, H. Weinstein, et al. Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes Blood, November 1, 2004; 104(9): 2646 - 2654. [Abstract] [Full Text] [PDF] J. J. Clark, J. Cools, D. P. Curley, J.-C. Yu, N. A. Lokker, N. A. Giese, and D. G. Gilliland Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518 Blood, November 1, 2004; 104(9): 2867 - 2872. [Abstract] [Full Text] [PDF] I. J. Griswold, L. J. Shen, P. La Rosee, S. Demehri, M. C. Heinrich, R. M. Braziel, L. McGreevey, A. D. Haley, N. Giese, B. J. Druker, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis Blood, November 1, 2004; 104(9): 2912 - 2918. [Abstract] [Full Text] [PDF] Y. Li, H. Li, M.-N. Wang, D. Lu, R. Bassi, Y. Wu, H. Zhang, P. Balderes, D. L. Ludwig, B. Pytowski, et al. Suppression of leukemia expressing wild-type or ITD-mutant FLT3 receptor by a fully human anti-FLT3 neutralizing antibody Blood, August 15, 2004; 104(4): 1137 - 1144. [Abstract] [Full Text] [PDF] S. Takahashi, M. J. McConnell, H. Harigae, M. Kaku, T. Sasaki, A. M. Melnick, and J. D. Licht The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT Blood, June 15, 2004; 103(12): 4650 - 4658. [Abstract] [Full Text] [PDF] B. D. Smith, M. Levis, M. Beran, F. Giles, H. Kantarjian, K. Berg, K. M. Murphy, T. Dauses, J. Allebach, and D. Small Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia Blood, May 15, 2004; 103(10): 3669 - 3676. [Abstract] [Full Text] [PDF] C. Muller-Tidow, B. Steffen, T. Cauvet, L. Tickenbrock, P. Ji, S. Diederichs, B. Sargin, G. Kohler, M. Stelljes, E. Puccetti, et al. Translocation Products in Acute Myeloid Leukemia Activate the Wnt Signaling Pathway in Hematopoietic Cells Mol. Cell. Biol., April 1, 2004; 24(7): 2890 - 2904. [Abstract] [Full Text] [PDF] K. Bagrintseva, R. Schwab, T. M. Kohl, S. Schnittger, S. Eichenlaub, J. W. Ellwart, W. Hiddemann, and K. Spiekermann Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells Blood, March 15, 2004; 103(6): 2266 - 2275. [Abstract] [Full Text] [PDF] R. Zheng, A. D. Friedman, M. Levis, L. Li, E. G. Weir, and D. Small Internal tandem duplication mutation of FLT3 blocks myeloid differentiation through suppression of C/EBP{alpha} expression Blood, March 1, 2004; 103(5): 1883 - 1890. [Abstract] [Full Text] [PDF] L.-Y. Shih, C.-F. Huang, J.-H. Wu, P.-N. Wang, T.-L. Lin, P. Dunn, M.-C. Chou, M.-C. Kuo, and C.-C. Tang Heterogeneous Patterns of FLT3 Asp835 Mutations in Relapsed de Novo Acute Myeloid Leukemia: A Comparative Analysis of 120 Paired Diagnostic and Relapse Bone Marrow Samples Clin. Cancer Res., February 15, 2004; 10(4): 1326 - 1332. [Abstract] [Full Text] [PDF] T. Taketani, T. Taki, K. Sugita, Y. Furuichi, E. Ishii, R. Hanada, M. Tsuchida, K. Sugita, K. Ida, and Y. Hayashi FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy Blood, February 1, 2004; 103(3): 1085 - 1088. [Abstract] [Full Text] [PDF] D. W. Sternberg and D. G. Gilliland The Role of Signal Transducer and Activator of Transcription Factors in Leukemogenesis J. Clin. Oncol., January 15, 2004; 22(2): 361 - 371. [Abstract] [Full Text] [PDF] J. E. Lancet and J. E. Karp Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy Blood, December 1, 2003; 102(12): 3880 - 3889. [Abstract] [Full Text] [PDF] A.-M. O'Farrell, J. M. Foran, W. Fiedler, H. Serve, R. L. Paquette, M. A. Cooper, H. A. Yuen, S. G. Louie, H. Kim, S. Nicholas, et al. An Innovative Phase I Clinical Study Demonstrates Inhibition of FLT3 Phosphorylation by SU11248 in Acute Myeloid Leukemia Patients Clin. Cancer Res., November 15, 2003; 9(15): 5465 - 5476. [Abstract] [Full Text] [PDF] W. Fiedler, R. Mesters, H. Tinnefeld, S. Loges, P. Staib, U. Duhrsen, M. Flasshove, O. G. Ottmann, W. Jung, F. Cavalli, et al. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia Blood, October 15, 2003; 102(8): 2763 - 2767. [Abstract] [Full Text] [PDF] Y. Minami, K. Yamamoto, H. Kiyoi, R. Ueda, H. Saito, and T. Naoe Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia Blood, October 15, 2003; 102(8): 2969 - 2975. [Abstract] [Full Text] [PDF] Q. Yao, R. Nishiuchi, Q. Li, A. R. Kumar, W. A. Hudson, and J. H. Kersey FLT3 Expressing Leukemias Are Selectively Sensitive to Inhibitors of the Molecular Chaperone Heat Shock Protein 90 through Destabilization of Signal Transduction-Associated Kinases Clin. Cancer Res., October 1, 2003; 9(12): 4483 - 4493. [Abstract] [Full Text] [PDF] C. M. Zwaan, S. Meshinchi, J. P. Radich, A. J. P. Veerman, D. R. Huismans, L. Munske, M. Podleschny, K. Hahlen, R. Pieters, M. Zimmermann, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance Blood, October 1, 2003; 102(7): 2387 - 2394. [Abstract] [Full Text] [PDF] K. Murata, H. Kumagai, T. Kawashima, K. Tamitsu, M. Irie, H. Nakajima, S. Suzu, M. Shibuya, S. Kamihira, T. Nosaka, et al. Selective Cytotoxic Mechanism of GTP-14564, a Novel Tyrosine Kinase Inhibitor in Leukemia Cells Expressing a Constitutively Active Fms-like Tyrosine Kinase 3 (FLT3) J. Biol. Chem., August 29, 2003; 278(35): 32892 - 32898. [Abstract] [Full Text] [PDF] S. Meshinchi, D. L. Stirewalt, T. A. Alonzo, Q. Zhang, D. A. Sweetser, W. G. Woods, I. D. Bernstein, R. J. Arceci, and J. P. Radich Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia Blood, August 15, 2003; 102(4): 1474 - 1479. [Abstract] [Full Text] [PDF] C. R. Antonescu, G. Sommer, L. Sarran, S. J. Tschernyavsky, E. Riedel, J. M. Woodruff, M. Robson, R. Maki, M. F. Brennan, M. Ladanyi, et al. Association of KIT Exon 9 Mutations with Nongastric Primary Site and Aggressive Behavior: KIT Mutation Analysis and Clinical Correlates of 120 Gastrointestinal Stromal Tumors Clin. Cancer Res., August 1, 2003; 9(9): 3329 - 3337. [Abstract] [Full Text] [PDF] F. J. Giles, A. T. Stopeck, L. R. Silverman, J. E. Lancet, M. A. Cooper, A. L. Hannah, J. M. Cherrington, A.-M. O'Farrell, H. A. Yuen, S. G. Louie, et al. SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes Blood, August 1, 2003; 102(3): 795 - 801. [Abstract] [Full Text] [PDF] R. Grundler, C. Thiede, C. Miething, C. Steudel, C. Peschel, and J. Duyster Sensitivity toward tyrosine kinase inhibitors varies between different activating mutations of the FLT3 receptor Blood, July 15, 2003; 102(2): 646 - 651. [Abstract] [Full Text] [PDF] K. Spiekermann, K. Bagrintseva, R. Schwab, K. Schmieja, and W. Hiddemann Overexpression and Constitutive Activation of FLT3 Induces STAT5 Activation in Primary Acute Myeloid Leukemia Blast Cells Clin. Cancer Res., June 1, 2003; 9(6): 2140 - 2150. [Abstract] [Full Text] [PDF] P. M. Chan, S. Ilangumaran, J. La Rose, A. Chakrabartty, and R. Rottapel Autoinhibition of the Kit Receptor Tyrosine Kinase by the Cytosolic Juxtamembrane Region Mol. Cell. Biol., May 1, 2003; 23(9): 3067 - 3078. [Abstract] [Full Text] [PDF] A.-M. O'Farrell, T. J. Abrams, H. A. Yuen, T. J. Ngai, S. G. Louie, K. W. H. Yee, L. M. Wong, W. Hong, L. B. Lee, A. Town, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo Blood, May 1, 2003; 101(9): 3597 - 3605. [Abstract] [Full Text] [PDF] M. Benekli, M. R. Baer, H. Baumann, and M. Wetzler Signal transducer and activator of transcription proteins in leukemias Blood, April 15, 2003; 101(8): 2940 - 2954. [Abstract] [Full Text] [PDF] M. Mizuki, J. Schwable, C. Steur, C. Choudhary, S. Agrawal, B. Sargin, B. Steffen, I. Matsumura, Y. Kanakura, F. D. Bohmer, et al. Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations Blood, April 15, 2003; 101(8): 3164 - 3173. [Abstract] [Full Text] [PDF] K. Spiekermann, R. J. Dirschinger, R. Schwab, K. Bagrintseva, F. Faber, C. Buske, S. Schnittger, L. M. Kelly, D. G. Gilliland, and W. Hiddemann The protein tyrosine kinase inhibitor SU5614 inhibits FLT3 and induces growth arrest and apoptosis in AML-derived cell lines expressing a constitutively activated FLT3 Blood, February 15, 2003; 101(4): 1494 - 1504. [Abstract] [Full Text] [PDF] F. D. Bohmer, L. Karagyozov, A. Uecker, H. Serve, A. Botzki, S. Mahboobi, and S. Dove A Single Amino Acid Exchange Inverts Susceptibility of Related Receptor Tyrosine Kinases for the ATP Site Inhibitor STI-571 J. Biol. Chem., February 7, 2003; 278(7): 5148 - 5155. [Abstract] [Full Text] [PDF] S. Frohling, R. F. Schlenk, J. Breitruck, A. Benner, S. Kreitmeier, K. Tobis, H. Dohner, and K. Dohner Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm Blood, December 15, 2002; 100(13): 4372 - 4380. [Abstract] [Full Text] [PDF] M. L. Guzman, C. F. Swiderski, D. S. Howard, B. A. Grimes, R. M. Rossi, S. J. Szilvassy, and C. T. Jordan Preferential induction of apoptosis for primary human leukemic stem cells PNAS, December 10, 2002; 99(25): 16220 - 16225. [Abstract] [Full Text] [PDF] R. Zheng, A. D. Friedman, and D. Small Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dcl3 cells caused by expression of FLT3/ITD mutations Blood, December 1, 2002; 100(12): 4154 - 4161. [Abstract] [Full Text] [PDF] R. L. Darley, L. Pearn, N. Omidvar, M. Sweeney, J. Fisher, S. Phillips, T. Hoy, and A. K. Burnett Protein kinase C mediates mutant N-Ras-induced developmental abnormalities in normal human erythroid cells Blood, December 1, 2002; 100(12): 4185 - 4192. [Abstract] [Full Text] [PDF] K. Spiekermann, K. Bagrintseva, C. Schoch, T. Haferlach, W. Hiddemann, and S. Schnittger A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia Blood, October 16, 2002; 100(9): 3423 - 3425. [Abstract] [Full Text] [PDF]

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