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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.

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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.


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Who's dancing with FLT3?
Mark Levis
Blood 2008 111: 2503-2504. [Full Text] [PDF]





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