SEARCH:   Advanced

Blood, 1 March 2004, Vol. 103, No. 5, pp. 1901-1908. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-06-1845. This Article Full Text (PDF) All Versions of this Article: 2003-06-1845v1 103/5/1901    most recent Alert me when this article is cited Alert me if a correction is posted 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 Ozeki, K. Articles by Naoe, T. Search for Related Content PubMed PubMed Citation Articles by Ozeki, K. Articles by Naoe, T. Social Bookmarking                   What's this? Submitted June 9, 2003 Accepted October 31, 2003 Biological and clinical significance of the FLT3 transcript level in acute myeloid leukemia Kazutaka Ozeki, Hitoshi Kiyoi*, Yuka Hirose, Masanori Iwai, Manabu Ninomiya, Yoshihisa Kodera, Shuichi Miyawaki, Kazutaka Kuriyama, Chihiro Shimazaki, Hideki Akiyama, Miki Nishimura, Toshiko Motoji, Katsuji Shinagawa, Akihiro Takeshita, Ryuzo Ueda, Ryuzo Ohno, Nobuhiko Emi, and Tomoki Naoe Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan Department of Medicine, Saiseikai Maebashi Hospital, Maebashi, Japan Research and Development Center for Higher Education, Nagasaki University, Nagasaki, Japan Department of Hematology, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Hematology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan Second Department of Internal medicine, Chiba University School of Medicine, Chiba, Japan Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan Second Department of Internal Medicine, Okayama University School of Medicine, Okayama, Japan Department of Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan Department of Internal Medicine and Molecular Science, Nagoya City University School of Medicine, Nagoya, Japan Aichi Cancer Center, Nagoya, Japan * Corresponding author; email: kiyoi{at}med.nagoya-u.ac.jp. Although FLT3 mutations are essentially found in myeloid-lineage leukemia cells, a high level of FLT3 expression was recently observed in MLL gene-rearranged acute lymphoblastic leukemia without FLT3 mutations. Here, we analyzed the biological and clinical significance of the FLT3 transcript level in comparison with several gene alterations in 181 de novo acute myeloid leukemia (AML) cases. The mean expression level in AML was higher than that in normal mononuclear cells, while the range varied widely. A high level of FLT3 is related to internal tandem duplication of the FLT3 gene (FLT3/ITD), the mutations within the activation loop of FLT3 (FLT3/D835Mt) and tandem duplication of the MLL gene (MLL-TD), but not to p53 or N-RAS gene mutations. Furthermore, a high expression level in AML cases with FLT3 mutations was not related to MLL-TD. Overexpressed FLT3 revealed auto-phosphorylation, and had the same sensitivity to the FLT3 inhibitor as FLT3/ITD. Overexpression of FLT3 (over 200,000 copies/µgRNA) was an unfavorable prognostic factor for overall survival in 91 AML cases without FLT3/ITD. These results indicated that FLT3 overexpression may distinguish a novel disease entity in AML without FLT3 mutations and serve as a therapeutic target for FLT3 inhibitors. 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] S. Meshinchi and F. R. Appelbaum Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia Clin. Cancer Res., July 1, 2009; 15(13): 4263 - 4269. [Abstract] [Full Text] [PDF] K. W. Pratz, J. Cortes, G. J. Roboz, N. Rao, O. Arowojolu, A. Stine, Y. Shiotsu, A. Shudo, S. Akinaga, D. Small, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response Blood, April 23, 2009; 113(17): 3938 - 3946. [Abstract] [Full Text] [PDF] R. W. Stam, P. Schneider, P. de Lorenzo, M. G. Valsecchi, M. L. den Boer, and R. Pieters Prognostic significance of high-level FLT3 expression in MLL-rearranged infant acute lymphoblastic leukemia Blood, October 1, 2007; 110(7): 2774 - 2775. [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] F. P.G. Silva, A. Lind, G. Brouwer-Mandema, P. J.M. Valk, and M. Giphart-Gassler Trisomy 13 correlates with RUNX1 mutation and increased FLT3 expression in AML-M0 patients Haematologica, August 1, 2007; 92(8): 1123 - 1126. [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] E. Morgado, S. Albouhair, and C. Lavau Flt3 is dispensable to the Hoxa9/Meis1 leukemogenic cooperation Blood, May 1, 2007; 109(9): 4020 - 4022. [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] 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. S. Wilson, G. S. Davidson, S. B. Martin, E. Andries, J. Potter, R. Harvey, K. Ar, Y. Xu, K. J. Kopecky, D. P. Ankerst, et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction Blood, July 15, 2006; 108(2): 685 - 696. [Abstract] [Full Text] [PDF] A. Pellagatti, M. Cazzola, A. A. N. Giagounidis, L. Malcovati, M. G. D. Porta, S. Killick, L. J. Campbell, L. Wang, C. F. Langford, C. Fidler, et al. Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype Blood, July 1, 2006; 108(1): 337 - 345. [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] 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] 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] 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] G. F. V. Woude, G. J. Kelloff, R. W. Ruddon, H.-M. Koo, C. C. Sigman, J. C. Barrett, R. W. Day, A. P. Dicker, R. S. Kerbel, D. R. Parkinson, et al. Reanalysis of Cancer Drugs: Old Drugs, New Tricks Clin. Cancer Res., June 1, 2004; 10(11): 3897 - 3907. [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020