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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0953. This Article Full Text (PDF) All Versions of this Article: 2002-03-0953v1 100/9/3423    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 Spiekermann, K. Articles by Schnittger, S. Search for Related Content PubMed PubMed Citation Articles by Spiekermann, K. Articles by Schnittger, S. Social Bookmarking                   What's this? Submitted March 27, 2002 Accepted June 13, 2002 A new and recurrent activating length mutation in exon 20 of the flt3 gene in acute myeloid leukemia Karsten Spiekermann*, Ksenia Bagrintseva, Claudia Schoch, Torsten Haferlach, Wolfgang Hiddemann, and Susanne Schnittger Clinical Cooperative Group, GSF-National Research Center for Environment and Health, Munich, Germany; Department of Medicine III, University Hospital Grosshadern, Munich, Germany Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Munich, Germany; Department of Medicine III, University Hospital Grosshadern, Munich, Germany Clinical Cooperative Group, GSF-National Research Center for Environment and Health, Munich, Germany; Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Munich, Germany; Department of Medicine III, University Hospital Grosshadern, Munich, Germany * Corresponding author; email: kspieke{at}gwdg.de. Activating length mutations in the juxtamembrane (JM) domain of the FLT3 gene (FLT3-LM) and mutations in the catalytic domain (FLT3D835/836) of this receptor tyrosine kinase represent the most frequent genetic alterations in acute myeloid leukemia (AML). Here, we describe a six base pair (bp) insertion in the activation loop of FLT3 between codons 840 and 841 of FLT3 (FLT3-840GS) in two unrelated patients with AML. Screening for other activating mutations of FLT3, CKIT and NRAS showed no further genetic alterations in patients carrying the FLT3-840GS. In functional analyses we could show that this mutant is hyperphosphorylated on tyrosine and confers IL-3 independent growth to Ba/F3 cells which can be inhibited by a specific FLT3 PTK inhibitor. Our results show for the first time that in addition to known mutations in the JM and the catalytic domain, further activating length mutations exist in the FLT3 gene. 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