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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.
 Previous Article | Next Article 
Submitted May 18, 2007
Accepted October 21, 2007
Prognostic relevance of FLT3-TKD mutations in AML:
the combination matters - an analysis of 3082 patients
Ulrike Bacher, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach, and Susanne Schnittger*
University Hospital of Hamburg-Eppendorf, Stem Cell Transplantation, Hamburg, Germany
MLL Munich Leukemia Laboratory, Munich, Germany
* Corresponding author; email: susanne.schnittger{at}mll-online.com.
We characterized the mutation 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 (88/1472; 6.0%). FLT3-TKD mutations were most frequent in the AML FAB subtypes M5b (15/114; 13.2%), M3v (6/51; 11.8%), and M4 (39/484; 8.1%). Similar to FLT3-LM the FLT3-TKD mutations show elevated peripheral leukocytes as compared to FLT3wt AML. FLT3-TKD had a high incidence in cases with NPM1 mutations (23/262; 8.8%), CEPBA mutations (6/76; 7.9%), and NRAS mutations (6/78; 7.7%). FLT3-TKD in combination with FLT3-LM (17/594 patients; 2.9%) and KITD816 (1/44; 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 CEPBA mutations.
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