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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, 15 April 2001, Vol. 97, No. 8, pp. 2434-2439 NEOPLASIA Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies Yukiya Yamamoto, Hitoshi Kiyoi, Yasuyuki Nakano, Ritsuro Suzuki, Yoshihisa Kodera, Shuichi Miyawaki, Norio Asou, Kazutaka Kuriyama, Fumiharu Yagasaki, Chihiro Shimazaki, Hideki Akiyama, Kenji Saito, Miki Nishimura, Toshiko Motoji, Katsuji Shinagawa, Akihiro Takeshita, Hidehiko Saito, Ryuzo Ueda, Ryuzo Ohno, and Tomoki Naoe From the Department of Infectious Diseases and the First Department of Internal Medicine, Nagoya University School of Medicine; Division of Molecular Medicine, Aichi Cancer Center; the Department of Medicine, Japanese Red Cross Nagoya First Hospital; Second Department of Internal Medicine, Nagoya City University School of Medicine, Nagoya, Japan; Department of Medicine, Saiseikai Maebashi Hospital, Maebashi, Japan; Second Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan; Department of Hematology, Atomic Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan; First Department of Internal Medicine, Saitama Medical School, Saitama, Japan; Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Hematology, Tokyo Metropolitan Komagome Hospital; Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan; Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan; Second Department of Internal Medicine, Chiba University School of Medicine, Chiba, Japan; Second Department of Medicine, Okayama University School of Medicine, Okayama, Japan; and Department of Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan. Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML. © 2001 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: S. Kayser, R. F. Schlenk, M. C. Londono, F. Breitenbuecher, K. Wittke, J. 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Kanakura FIP1L1-PDGFR{alpha} Imposes Eosinophil Lineage Commitment on Hematopoietic Stem/Progenitor Cells J. Biol. Chem., March 20, 2009; 284(12): 7719 - 7732. [Abstract] [Full Text] [PDF] E. Weisberg, J. Roesel, G. Bold, P. Furet, J. Jiang, J. Cools, R. D. Wright, E. Nelson, R. Barrett, A. Ray, et al. Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells Blood, December 15, 2008; 112(13): 5161 - 5170. [Abstract] [Full Text] [PDF] G. Marcucci, K. Maharry, M. D. Radmacher, K. Mrozek, T. Vukosavljevic, P. Paschka, S. P. Whitman, C. Langer, C. D. Baldus, C.-G. Liu, et al. Prognostic Significance of, and Gene and MicroRNA Expression Signatures Associated With, CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia With High-Risk Molecular Features: A Cancer and Leukemia Group B Study J. Clin. Oncol., November 1, 2008; 26(31): 5078 - 5087. [Abstract] [Full Text] [PDF] C. K. Cheng, L. Li, S. H. Cheng, K. M. Lau, N. P. H. Chan, R. S. M. Wong, M. M. K. Shing, C. K. Li, and M. H. L. Ng Transcriptional repression of the RUNX3/AML2 gene by the t(8;21) and inv(16) fusion proteins in acute myeloid leukemia Blood, October 15, 2008; 112(8): 3391 - 3402. [Abstract] [Full Text] [PDF] P. Paschka, G. Marcucci, A. S. Ruppert, S. P. Whitman, K. Mrozek, K. Maharry, C. Langer, C. D. Baldus, W. Zhao, B. L. Powell, et al. Wilms' Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., October 1, 2008; 26(28): 4595 - 4602. [Abstract] [Full Text] [PDF] J. P. Radich Molecular Classification of Acute Myeloid Leukemia: Are We There Yet? J. Clin. Oncol., October 1, 2008; 26(28): 4539 - 4541. [Full Text] [PDF] J. Laubach and A. V. Rao Current and Emerging Strategies for the Management of Acute Myeloid Leukemia in the Elderly Oncologist, October 1, 2008; 13(10): 1097 - 1108. 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High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study Blood, June 1, 2008; 111(11): 5371 - 5379. [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] R. F. Schlenk, K. Dohner, J. Krauter, S. Frohling, A. Corbacioglu, L. Bullinger, M. Habdank, D. Spath, M. Morgan, A. Benner, et al. Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1909 - 1918. [Abstract] [Full Text] [PDF] M. M. Loriaux, R. L. Levine, J. W. Tyner, S. Frohling, C. Scholl, E. P. Stoffregen, G. Wernig, H. Erickson, C. A. Eide, R. Berger, et al. High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia Blood, May 1, 2008; 111(9): 4788 - 4796. [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] B. V. Balgobind, P. Van Vlierberghe, A. M. W. van den Ouweland, H. B. Beverloo, J. N. R. Terlouw-Kromosoeto, E. R. van Wering, D. Reinhardt, M. Horstmann, G. J. L. Kaspers, R. Pieters, et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis Blood, April 15, 2008; 111(8): 4322 - 4328. [Abstract] [Full Text] [PDF] E. Weisberg, L. Banerji, R. D. Wright, R. Barrett, A. Ray, D. Moreno, L. Catley, J. Jiang, E. Hall-Meyers, M. Sauveur-Michel, et al. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells Blood, April 1, 2008; 111(7): 3723 - 3734. [Abstract] [Full Text] [PDF] A. Torkamani and N. J. Schork Prediction of Cancer Driver Mutations in Protein Kinases Cancer Res., March 15, 2008; 68(6): 1675 - 1682. [Abstract] [Full Text] [PDF] R. Monni, L. Haddaoui, A. Naba, I. Gallais, M. Arpin, P. Mayeux, and F. Moreau-Gachelin Ezrin is a target for oncogenic Kit mutants in murine erythroleukemia Blood, March 15, 2008; 111(6): 3163 - 3172. [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] X.-F. Huang, S.-K. Luo, J. Xu, J. Li, D.-R. Xu, L.-H. Wang, M. Yan, X.-R. Wang, X.-B. Wan, F.-M. Zheng, et al. Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia Blood, March 1, 2008; 111(5): 2854 - 2865. [Abstract] [Full Text] [PDF] J. W. Tyner, D. K. Walters, S. G. Willis, M. Luttropp, J. Oost, M. Loriaux, H. Erickson, A. S. Corbin, T. O'Hare, M. C. Heinrich, et al. RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2238 - 2245. [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] 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] A. Pradhan, Q. T. Lambert, and G. W. Reuther Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor PNAS, November 20, 2007; 104(47): 18502 - 18507. [Abstract] [Full Text] [PDF] A. C.H. de Vries, R. W. Stam, P. Schneider, C. M. Niemeyer, E. R. van Wering, O. A. Haas, C. P. Kratz, M. L. den Boer, R. Pieters, and M. M. van den Heuvel-Eibrink Role of mutation independent constitutive activation of FLT3 in juvenile myelomonocytic leukemia Haematologica, November 1, 2007; 92(11): 1557 - 1560. [Abstract] [Full Text] [PDF] Y. Furuichi, K. Goi, T. Inukai, H. Sato, A. Nemoto, K. Takahashi, K. Akahane, K. Hirose, H. Honna, I. Kuroda, et al. Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces MLL-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents Cancer Res., October 15, 2007; 67(20): 9852 - 9861. [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] F. Dicker, C. Haferlach, W. Kern, T. Haferlach, and S. Schnittger Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia Blood, August 15, 2007; 110(4): 1308 - 1316. [Abstract] [Full Text] [PDF] H. Kiyoi, Y. Shiotsu, K. Ozeki, S. Yamaji, H. Kosugi, H. Umehara, M. Shimizu, H. Arai, K. Ishii, S. Akinaga, et al. A Novel FLT3 Inhibitor FI-700 Selectively Suppresses the Growth of Leukemia Cells with FLT3 Mutations Clin. Cancer Res., August 1, 2007; 13(15): 4575 - 4582. [Abstract] [Full Text] [PDF] L. F. Peterson, A. Boyapati, E.-Y. Ahn, J. R. Biggs, A. J. Okumura, M.-C. Lo, M. Yan, and D.-E. Zhang Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts Blood, August 1, 2007; 110(3): 799 - 805. [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] E. Weisberg, A. L. Kung, R. D. Wright, D. Moreno, L. Catley, A. Ray, L. Zawel, M. Tran, J. Cools, G. Gilliland, et al. Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells Mol. Cancer Ther., July 1, 2007; 6(7): 1951 - 1961. [Abstract] [Full Text] [PDF] U. Bacher, T. Haferlach, W. Kern, C. Haferlach, and S. Schnittger A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia Haematologica, June 1, 2007; 92(6): 744 - 752. [Abstract] [Full Text] [PDF] C. Graf, F. Heidel, S. Tenzer, M. P. Radsak, F. K. Solem, C. M. Britten, C. Huber, T. Fischer, and T. Wolfel A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells Blood, April 1, 2007; 109(7): 2985 - 2988. [Abstract] [Full Text] [PDF] S. Meshinchi and R. J. Arceci Prognostic Factors and Risk-Based Therapy in Pediatric Acute Myeloid Leukemia Oncologist, March 1, 2007; 12(3): 341 - 355. [Abstract] [Full Text] [PDF] O. Piloto, M. Wright, P. Brown, K.-T. Kim, M. Levis, and D. Small Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways Blood, February 15, 2007; 109(4): 1643 - 1652. [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] 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] S. Knapper, A. K. Burnett, T. Littlewood, W. J. Kell, S. Agrawal, R. Chopra, R. Clark, M. J. Levis, and D. Small A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy Blood, November 15, 2006; 108(10): 3262 - 3270. [Abstract] [Full Text] [PDF] S. Knapper, K. I. Mills, A. F. Gilkes, S. J. Austin, V. Walsh, and A. K. Burnett The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases Blood, November 15, 2006; 108(10): 3494 - 3503. [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] 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] O. Piloto, B. Nguyen, D. Huso, K.-T. Kim, Y. Li, L. Witte, D. J. Hicklin, P. Brown, and D. Small IMC-EB10, an Anti-FLT3 Monoclonal Antibody, Prolongs Survival and Reduces Nonobese Diabetic/Severe Combined Immunodeficient Engraftment of Some Acute Lymphoblastic Leukemia Cell Lines and Primary Leukemic Samples. Cancer Res., May 1, 2006; 66(9): 4843 - 4851. [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] R. Cairoli, A. Beghini, G. Grillo, G. Nadali, F. Elice, C. B. Ripamonti, P. Colapietro, M. Nichelatti, L. Pezzetti, M. Lunghi, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study Blood, May 1, 2006; 107(9): 3463 - 3468. [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] A. Shimada, T. Taki, K. Tabuchi, A. Tawa, K. Horibe, M. Tsuchida, R. Hanada, I. Tsukimoto, and Y. Hayashi KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group Blood, March 1, 2006; 107(5): 1806 - 1809. [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] D. Small FLT3 Mutations: Biology and Treatment Hematology, January 1, 2006; 2006(1): 178 - 184. [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] X. Lu, R. Levine, W. Tong, G. Wernig, Y. Pikman, S. Zarnegar, D. G. Gilliland, and H. Lodish Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation PNAS, December 27, 2005; 102(52): 18962 - 18967. [Abstract] [Full Text] [PDF] P. Van Vlierberghe, J. P. P. Meijerink, R. W. Stam, W. van der Smissen, E. R. van Wering, H. B. Beverloo, and R. Pieters Activating FLT3 mutations in CD4+/CD8- pediatric T-cell acute lymphoblastic leukemias Blood, December 15, 2005; 106(13): 4414 - 4415. [Full Text] [PDF] R. E. Gale, R. Hills, A. R. Pizzey, P. D. Kottaridis, D. Swirsky, A. F. Gilkes, E. Nugent, K. I. Mills, K. Wheatley, E. Solomon, et al. Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia Blood, December 1, 2005; 106(12): 3768 - 3776. [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] T. Suzuki, H. Kiyoi, K. Ozeki, A. Tomita, S. Yamaji, R. Suzuki, Y. Kodera, S. Miyawaki, N. Asou, K. Kuriyama, et al. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia Blood, October 15, 2005; 106(8): 2854 - 2861. [Abstract] [Full Text] [PDF] R. W. Stam, M. L. den Boer, P. Schneider, P. Nollau, M. Horstmann, H. B. Beverloo, E. van der Voort, M. G. Valsecchi, P. de Lorenzo, S. E. Sallan, et al. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia Blood, October 1, 2005; 106(7): 2484 - 2490. [Abstract] [Full Text] [PDF] D. T. Bowen, M. E. Frew, R. Hills, R. E. Gale, K. Wheatley, M. J. Groves, S. E. Langabeer, P. D. Kottaridis, A. V. Moorman, A. K. Burnett, et al. RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years Blood, September 15, 2005; 106(6): 2113 - 2119. [Abstract] [Full Text] [PDF] S. Frohling, C. Scholl, D. G. Gilliland, and R. L. Levine Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications J. Clin. Oncol., September 10, 2005; 23(26): 6285 - 6295. [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] D. E. Lopes de Menezes, J. Peng, E. N. Garrett, S. G. Louie, S. H. Lee, M. Wiesmann, Y. Tang, L. Shephard, C. Goldbeck, Y. Oei, et al. CHIR-258: A Potent Inhibitor of FLT3 Kinase in Experimental Tumor Xenograft Models of Human Acute Myelogenous Leukemia Clin. Cancer Res., July 15, 2005; 11(14): 5281 - 5291. [Abstract] [Full Text] [PDF] D. S. Krause and R. A. Van Etten Tyrosine Kinases as Targets for Cancer Therapy N. Engl. J. Med., July 14, 2005; 353(2): 172 - 187. [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] 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] D. K. Walters, E. P. Stoffregen, M. C. Heinrich, M. W. Deininger, and B. J. Druker RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518 Blood, April 1, 2005; 105(7): 2952 - 2954. [Abstract] [Full Text] [PDF] C. Recher, O. Beyne-Rauzy, C. Demur, G. Chicanne, C. Dos Santos, V. M.-D. Mas, D. Benzaquen, G. Laurent, F. Huguet, and B. Payrastre Antileukemic activity of rapamycin in acute myeloid leukemia Blood, March 15, 2005; 105(6): 2527 - 2534. [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] O. Piloto, M. Levis, D. Huso, Y. Li, H. Li, M.-N. Wang, R. Bassi, P. Balderes, D. L. Ludwig, L. Witte, et al. Inhibitory Anti-FLT3 Antibodies Are Capable of Mediating Antibody-Dependent Cell-Mediated Cytotoxicity and Reducing Engraftment of Acute Myelogenous Leukemia Blasts in Nonobese Diabetic/Severe Combined Immunodeficient Mice Cancer Res., February 15, 2005; 65(4): 1514 - 1522. [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] R. M. Stone, D. J. DeAngelo, V. Klimek, I. Galinsky, E. Estey, S. D. Nimer, W. Grandin, D. Lebwohl, Y. Wang, P. Cohen, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412 Blood, January 1, 2005; 105(1): 54 - 60. [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] 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] F. Chiara, M.-J. Goumans, H. Forsberg, A. Ahgren, A. Rasola, P. Aspenstrom, C. Wernstedt, C. Hellberg, C.-H. Heldin, and R. Heuchel A Gain of Function Mutation in the Activation Loop of Plateletderived Growth Factor {beta}-Receptor Deregulates Its Kinase Activity J. Biol. Chem., October 8, 2004; 279(41): 42516 - 42527. [Abstract] [Full Text] [PDF] P. Brown, S. Meshinchi, M. Levis, T. A. Alonzo, R. Gerbing, B. Lange, R. Arceci, and D. Small Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed by FLT3 inhibition Blood, September 15, 2004; 104(6): 1841 - 1849. [Abstract] [Full Text] [PDF] J. Jiang, J. G. Paez, J. C. Lee, R. Bo, R. M. Stone, D. J. DeAngelo, I. Galinsky, B. M. Wolpin, A. Jonasova, P. Herman, et al. Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML Blood, September 15, 2004; 104(6): 1855 - 1858. [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] M. Levis, R. Pham, B. D. Smith, and D. Small In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects Blood, August 15, 2004; 104(4): 1145 - 1150. [Abstract] [Full Text] [PDF] R. Luthra and L. J. Medeiros Isothermal Multiple Displacement Amplification: A Highly Reliable Approach for Generating Unlimited High Molecular Weight Genomic DNA from Clinical Specimens J. Mol. Diagn., August 1, 2004; 6(3): 236 - 242. [Abstract] [Full Text] J. Chen, I. R. Williams, J. L. Kutok, N. Duclos, E. Anastasiadou, S. C. Masters, H. Fu, and D. G. Gilliland Positive and negative regulatory roles of the WW-like domain in TEL-PDGF{beta}R transformation Blood, July 15, 2004; 104(2): 535 - 542. [Abstract] [Full Text] [PDF] E. J. C. Rombouts, B. Pavic, B. Lowenberg, and R. E. Ploemacher Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia Blood, July 15, 2004; 104(2): 550 - 557. [Abstract] [Full Text] [PDF] E. Paietta, A. A. Ferrando, D. Neuberg, J. M. Bennett, J. Racevskis, H. Lazarus, G. Dewald, J. M. Rowe, P. H. Wiernik, M. S. Tallman, et al. Activating FLT3 mutations in CD117/KIT+ T-cell acute lymphoblastic leukemias Blood, July 15, 2004; 104(2): 558 - 560. [Abstract] [Full Text] [PDF]

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