FLT3 Gene Mutation Profile and Prognosis in Adult Acute Myeloid Leukemia.
BACKGROUND
Internal tandem duplication (ITD) of FMS-related tyrosine kinase 3 (FLT3) gene, which occurs in exons 14 and 15, is one of the most prevalent somatic mutations in adult acute myeloid leukemia (AML) and has biological, prognostic, and therapeutic implications. The prognostic importance of codon 835 tyrosine kinase domain (TKD) mutation (exon 20), which occurs relatively frequently in adult AML, is often debated. We aimed to study the FLT3 gene mutation profile and prognosis in 139 adult Iranian patients with newly diagnosed AML.


METHODS
We determined the status of ITD and TKD mutations using fragment analysis and the polymerase chain reaction-restriction fragment polymorphism method, respectively. In addition, we used direct sequencing to confirm the results of TKD mutation analysis.


RESULTS
Twenty five percent of the patients had an ITD mutation. The mean size of the inserted fragment was 63.5 base pairs. Twenty percent of the ITD-positive patients showed more than one mutated population upon polymerase chain reaction. Statistical analyses showed that the ITD mutation was associated with a decreased overall survival among patients in the intermediate cytogenetic risk group (p-value = 0.013). The size of the ITD was not correlated with overall survival. Eight out of 139 patients (5.7%) had the codon 835 mutation. One new mutation of the insertion/deletion type was discovered. Analyses did not show any relationship between the TKD mutation and overall survival. Two patients (1.4%) showed concurrent TKD and ITD mutations. The TKD and ITD mutation rates of the FLT3 gene were consistent with previous studies on AML patients.


CONCLUSIONS
This study supports the results of previous studies regarding the association of the FLT3-ITD mutation and poor prognosis.
Aileen
A
Azari-Yam
Javad
J
Tavakkoly-Bazzaz
Yousef
Y
Semnani
Elham
E
Davoudi-Dehaghani
Robabeh
R
Ghodssi-Ghassemabadi
Soodeh
S
Kianfar
Ameneh
A
Saadat
Mahboobeh
M
Masoudifard
Marjan
M
Yaghmaie
Kamran
K
Alimoghaddam
Ardeshir
A
Ghavamzadeh
Sirous
S
Zeinali
D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3