FMS-like tyrosine kinase 3 internal tandem duplication and the patterns of its gene sequence in 207 Chinese patients with de novo acute myeloid leukemia.
BACKGROUND
Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML).


OBJECTIVE
To study the patterns of FLT3-ITD in Chinese patients with AML.


METHODS
A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives.


RESULTS
A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML.


CONCLUSIONS
Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.
Department of Laboratory Medicine, West China Hospital, Sichuan University Chengdu, Sichuan, People's Republic of China.
Ling
L
Zhong
Yong Qian
YQ
Jia
Wen Tong
WT
Meng
Xun
X
Ni
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019011:Antigens, CD7 / Q000378:metabolism; D001483:Base Sequence; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences / Q000235:genetics*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D019011:Antigens, CD7; D019002:CD56 Antigen; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3