FLT3 overexpression in acute promyelocytic leukemia patients without detectable FLT3-ITD or codon 835-836 mutations: a pilot study.
BACKGROUND
Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking.


METHODS
Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease.


RESULTS
High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations.


CONCLUSIONS
FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.
Lilakos
K
K
First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, The Greek AML Study Group, Athens, Greece.
Viniou
N A
NA
Mavrogianni
D
D
Vassilakopoulos
T P
TP
Dimopoulou
M N
MN
Plata
E
E
Angelopoulou
M K
MK
Variami
E
E
Stavrogianni
N
N
Liapi
D
D
Xilouri
I
I
Galanopoulos
A
A
Ageloudi
M
M
Panayiotidis
P
P
Voulgarelis
M
M
Rombos
J
J
Meletis
J
J
Yataganas
X
X
Pangalis
G A
GA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D003062:Codon; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D010865:Pilot Projects; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis / Q000235:genetics*
D003062:Codon; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3