SEARCH:   Advanced

Blood, 15 April 2005, Vol. 105, No. 8, pp. 3319-3321. Prepublished online as a Blood First Edition Paper on December 23, 2004; DOI 10.1182/blood-2004-06-2068. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2068v1 105/8/3319    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 Kohl, T. M. Articles by Spiekermann, K. Search for Related Content PubMed PubMed Citation Articles by Kohl, T. M. Articles by Spiekermann, K. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report KIT exon 8 mutations associated with core-binding factor (CBF)–acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor Tobias M. Kohl, Susanne Schnittger, Joachim W. Ellwart, Wolfgang Hiddemann, and Karsten Spiekermann From the Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians University, Clinical Cooperative Group "Leukemia" and the Laboratory for Leukemia Diagnostics, GSF-National Research Center for Environment and Health, Munich, Germany. KIT exon 8 mutations are located in the extracellular portion of the receptor and are strongly associated with core-binding factor (CBF)-acute myeloid leukemia (AML). To characterize the functional role of these mutants, we analyzed the proproliferative and antiapoptotic potential of 3 KIT exon 8 mutations in interleukin 3 (IL-3)-dependent Ba/F3 cells. All KIT exon 8 mutants induced receptor hyperactivation in response to stem cell factor (SCF) stimulation in terms of proliferation and resistance toward apoptotic cell death. A representative KIT exon 8 mutant showed spontaneous receptor dimerization, phosphorylation of mitogen-activated protein kinase (MAPK), and conferred IL-3-independent growth to Ba/F3 cells. MAPK and phosphatidylinositol 3-kinase (PI3-kinase) activation was essential for the phenotype of this mutant. Additionally, imatinib inhibited proliferation of KIT exon 8 mutant-expressing Ba/F3 cells. Our data show that KIT exon 8 mutations represent gain-of-function mutations and might represent a new molecular target for treatment of CBF leukemias. (Blood. 2005;105:3319-3321) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] 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] J A Schumacher, K S J Elenitoba-Johnson, and M S Lim Detection of the c-kit D816V mutation in systemic mastocytosis by allele-specific PCR J. Clin. Pathol., January 1, 2008; 61(1): 109 - 114. [Abstract] [Full Text] [PDF] U. Testa and R. Riccioni Deregulation of apoptosis in acute myeloid leukemia Haematologica, January 1, 2007; 92(1): 81 - 94. [Abstract] [Full Text] [PDF] P. Paschka, G. Marcucci, A. S. Ruppert, K. Mrozek, H. Chen, R. A. Kittles, T. Vukosavljevic, D. Perrotti, J. W. Vardiman, A. J. Carroll, et al. Adverse Prognostic Significance of KIT Mutations in Adult Acute Myeloid Leukemia With inv(16) and t(8;21): A Cancer and Leukemia Group B Study J. Clin. Oncol., August 20, 2006; 24(24): 3904 - 3911. [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] S. Schnittger, T. M. Kohl, T. Haferlach, W. Kern, W. Hiddemann, K. Spiekermann, and C. Schoch KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival Blood, March 1, 2006; 107(5): 1791 - 1799. [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]

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