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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2527-2537. Prepublished online as a Blood First Edition Paper on October 26, 2007; DOI 10.1182/blood-2007-05-091215. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-091215v1 111/5/2527    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 Bacher, U. Articles by Schnittger, S. Search for Related Content PubMed PubMed Citation Articles by Bacher, U. Articles by Schnittger, S. Related Collections Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients Ulrike Bacher1, Claudia Haferlach2, Wolfgang Kern2, Torsten Haferlach2, and Susanne Schnittger2 1 Bone Marrow Transplant Unit, University Hospital of Hamburg-Eppendorf, Hamburg; and 2 Munich Leukemia Laboratory, Munich, Germany We characterized the mutational status of the FLT3 tyrosine kinase domain (FLT3-TLD) in 3082 patients with newly diagnosed AML. FLT3-TKD mutations were detected in 147 of 3082 (4.8%) patients. Similar to the FLT3 juxtamembrane domain mutations (FLT3-LM), there was a high correlation of FLT3-TKD mutations with normal karyotype (88 of 1472; 6.0%). FLT3-TKD mutations were most frequent in the AML FAB subtypes M5b (15 of 114; 13.2%), M3v (6 of 51; 11.8%), and M4 (39 of 484; 8.1%). Similar to FLT3-LM, the FLT3-TKD mutations show elevated peripheral leukocytes compared with FLT3wt AML. FLT3-TKD had a high incidence in cases with NPM1 mutations (23 of 262; 8.8%), CEBPA mutations (6 of 76; 7.9%), and NRAS mutations (6 of 78; 7.7%). FLT3-TKD in combination with FLT3-LM (17 of 594 patients; 2.9%) and KITD816 (1 of 44; 2.3%) was rare. Unlike the FLT3-LM, which are associated with inferior survival, prognosis was not influenced by FLT3-TKD in the total cohort of 1720 cases, where follow-up data were available (97 FLT3-TKD; 1623 FLT3-WT). In t(15;17)/PML-RARA with FLT3-TKD mutations, in FLT3-LM/TKD double-mutated, and in MLL-PTD/TKD double-mutated cases prognosis was unfavorably influenced by FLT3-TKD mutations. In contrast, we found an additional favorable impact of FLT3-TKD on EFS in prognostically favorable AML with NPM1- or CEBPA mutations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Who's dancing with FLT3? Mark Levis Blood 2008 111: 2503-2504. [Full Text] [PDF] This article has been cited by other articles: K. H. Metzeler, A. Dufour, T. Benthaus, M. Hummel, M.-C. Sauerland, A. Heinecke, W. E. Berdel, T. Buchner, B. Wormann, U. Mansmann, et al. ERG Expression Is an Independent Prognostic Factor and Allows Refined Risk Stratification in Cytogenetically Normal Acute Myeloid Leukemia: A Comprehensive Analysis of ERG, MN1, and BAALC Transcript Levels Using Oligonucleotide Microarrays J. Clin. Oncol., October 20, 2009; 27(30): 5031 - 5038. [Abstract] [Full Text] [PDF] C. Haferlach, C. Mecucci, S. Schnittger, A. Kohlmann, M. Mancini, A. Cuneo, N. Testoni, G. Rege-Cambrin, A. Santucci, M. Vignetti, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features Blood, October 1, 2009; 114(14): 3024 - 3032. [Abstract] [Full Text] [PDF] S. Schnittger, W. Kern, C. Tschulik, T. Weiss, F. Dicker, B. Falini, C. Haferlach, and T. Haferlach Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML Blood, September 10, 2009; 114(11): 2220 - 2231. [Abstract] [Full Text] [PDF] K. I. Mills, A. Kohlmann, P. M. Williams, L. Wieczorek, W.-m. Liu, R. Li, W. Wei, D. T. Bowen, H. Loeffler, J. M. Hernandez, et al. Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome Blood, July 30, 2009; 114(5): 1063 - 1072. [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] J. Hu, Y.-F. Liu, C.-F. Wu, F. Xu, Z.-X. Shen, Y.-M. Zhu, J.-M. Li, W. Tang, W.-L. Zhao, W. Wu, et al. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia PNAS, March 3, 2009; 106(9): 3342 - 3347. [Abstract] [Full Text] [PDF] S. Koschmieder, B. Halmos, E. Levantini, and D. G. Tenen Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer J. Clin. Oncol., February 1, 2009; 27(4): 619 - 628. [Abstract] [Full Text] [PDF] T. Buchner, W. E. Berdel, J. Kienast, A. Quintas-Cardama, W. Saber, E. C. Williams, H. Narimatsu, R. Schlenk, K. Dohner, and H. Dohner Cytogenetically normal acute myeloid leukemia. N. Engl. J. Med., August 7, 2008; 359(6): 651 - 652. [Full Text] [PDF] M. Raghavan, L.-L. Smith, D. M. Lillington, T. Chaplin, I. Kakkas, G. Molloy, C. Chelala, J.-B. Cazier, J. D. Cavenagh, J. Fitzgibbon, et al. Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia Blood, August 1, 2008; 112(3): 814 - 821. [Abstract] [Full Text] [PDF] T. Haferlach Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia Hematology, January 1, 2008; 2008(1): 400 - 411. [Abstract] [Full Text] [PDF]

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