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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0953.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3423-3425
BRIEF REPORT
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
From the Clinical Cooperative Group "Leukemia,"
GSF, National Research Center for Environment and Health, Laboratory
for Leukemia Diagnostics, and Department of Medicine III, University
Hospital Grosshadern, Ludwig-Maximilians University, Munich,
Germany.
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 6-bp insertion in the
activation loop of FLT3 between codons 840 and 841 of FLT3 (FLT3-840GS)
in 2 unrelated patients with AML. Screening for other activating
mutations of FLT3, KIT, 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 interleukin 3-independent
growth to Ba/F3 cells, which can be inhibited by a specific FLT3
protein tyrosine kinase (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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