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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2386-2392. Prepublished online as a Blood First Edition Paper on July 14, 2009; DOI 10.1182/blood-2009-03-209999. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2009-03-209999v1 114/12/2386    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 CrossRef Google Scholar Articles by Kayser, S. Articles by Döhner, K. PubMed PubMed Citation Articles by Kayser, S. Articles by Döhner, K. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome Sabine Kayser1, Richard F. Schlenk1, Martina Correa Londono1, Frank Breitenbuecher2, Kerstin Wittke1, Juan Du1, Silja Groner1, Daniela Späth1, Jürgen Krauter3, Arnold Ganser3, Hartmut Döhner1, Thomas Fischer4, Konstanze Döhner1, and for the German-Austrian AML Study Group (AMLSG) 1 Department of Internal Medicine III, University Hospital of Ulm, Ulm; 2 Department of Medicine (Cancer Research), University Hospital of Essen, Essen; 3 Department of Hematology, Hemostasis and Oncology, Hannover Medical School, Hannover; and 4 Department of Hematology/Oncology, Medical Center, Otto-von-Guericke University of Magdeburg, Magdeburg, Germany To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD–positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITD–mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD–positive AML. The clinical trials described herein have been registered as follows: AML HD93 (already published in 2003), AML HD98A (NCT00146120 [ClinicalTrials.gov] ; http://www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242 [ClinicalTrials.gov] ; http://www.ClinicalTrials.gov). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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