[FMS-like tyrosine kinase 3 gene mutations in acute myeloid leukemia].
This study was aimed to investigate the frequency of FMS-like tyrosine kinase 3 (FLT3) mutations including internal tandem duplication (ITD) mutation of juxtamembrane region and point mutation of the second tyrosine kinase domain (TKD) in acute myeloid leukemia (AML) patients and its clinical significance. The ITD mutation in FLT3 exon 14, 15 of bone marrow mononuclear cells was detected by genomic DNA-PCR, the TKD point mutation in FLT3 exon 20 was detected by genomic DNA-PCR combined with restriction endonuclease digest. The results indicated that among 131 newly diagnosed AML patients, 21 patients (16.0%) showed FLT3-ITD positive, 3 patients (2.3%) showed FLT3-TKD positive. None was found harboring both mutations. The WBC and bone marrow blast counts in FLT3-ITD positive patients seemed both higher than those in patients with wild-type FLT3 (FLT3-wt), but there was significant difference only in WBC count (p<0.05). The complete remission (CR) rate in FLT3-ITD positive patients was 47.6%, which was significantly lower than that in FLT3-wt patients (88.1%, p<0.05). There was no statistical difference in CR rate between FLT3-ITD positive and negative patients in 20 cases of M3; the CR rate in FLT3-ITD positive patients with non M(3) was 37.5 (6/16) which was obviously lower than that in FLT3-wt patients with non M3 (90.6%, 48/53) (p<0.05). 3 FLT3-ITD positive patients with CR relapsed after CR for 14 (2-20) months with relapse rate 50% (3/6) which was higher than that in FLT3-wt patients (29.2%, 14/48). It is concluded that FLT3 mutation is common in AML patients, while FLT3-ITD mutation is more frequent than FLT3-TKD mutation. The AML patients with FLT3-ITD mutation have a poor prognosis, while FLT3-TKD point mutation does not significantly influences prognosis of the patients. Therefore early detection of FLT3 mutation may be important for targeting therapy and evaluating clinical prognosis of AML patients.
Han
Yang-Li
YL
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Zhang
Su-Jiang
SJ
Qiao
Chun
C
Dai
Dan
D
Sun
Xue-Mei
XM
Xu
Yan-Li
YL
Qian
Si-Xuan
SX
Xu
Wei
W
Wang
Ji-Shi
JS
Li
Jian-Yong
JY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017434:Protein Structure, Tertiary; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3