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Int J Hematol. 2006 May;83(4):301-8.
Biology, clinical relevance, and
molecularly targeted therapy in acute leukemia with
FLT3 mutation.
Kiyoi
H, Naoe T.
Department of Infectious Diseases, Nagoya University
Graduate School of Medicine, Nagoya, Japan. kiyoi@med.nagoya-u.ac.jp
Overexpression and activating
mutations of receptor tyrosine kinases (RTKs) are
known to be involved in the pathophysiology of
several kinds of cancer cells. FMS-like receptor
tyrosine kinase 3 (FLT3), together with KIT, FMS,
and platelet-derived growth factor receptor, is a
class III RTK. FLT3 mutations were first reported as
internal tandem duplication (FLT3/ITD) of the
juxtamembrane domain-coding sequence; subsequently,
a missense point mutation at the D835 residue and
point mutations, deletions, and insertions in the
codons surrounding D835 within a FLT3 tyrosine
kinase domain (FLT3/KDMs) have been found. FLT3
mutations are the most frequent genetic alterations
so far reported in acute myeloid leukemia and are
involved in the signaling pathway of autonomous
proliferation and differentiation block in leukemia
cells. Several large-scale studies have confirmed
that FLT3/ITD is strongly associated with
leukocytosis and a poor prognosis. Therefore,
routine screening for FLT3 mutations is recommended
to stratify patients into distinct risk groups.
However, because high-dose chemotherapy and stem
cell transplantation cannot overcome the adverse
effects of FLT3 mutations, the development of FLT3
kinase inhibitors is expected to produce a more
efficacious therapeutic strategy for leukemia
therapy.
PMID: 16757428 [PubMed - indexed for
MEDLINE]