急性髓系白血病FLT3基因突变研究

本研究探讨急性髓系白血病（acute myeloid leukemia，AML）患者中FMS样酪氨酸激酶3（FLT3）基因内部串联重复突变（ITD）及第二酪氨酸激酶结构域（TKD）点突变及其临床意义。采用基因组DNA—PCR方法检测131例初发AML患者骨髓单个核细胞FLT3基因外显子14、15中ITD突变，采用基因组DNA—PCR结合限制性内切酶酶切方法检测FLT3基因外显子20中TKD点突变。结果表明：131例初治AML患者中，21例（16．0％）FLT3－ITD突变阳性，3例（2．3％）FLT3－TKD点突变阳性，无同一患者同时发生两种突变。FLT3－ITD阳性组初诊时白细胞计数（WBC）及骨髓原始细胞比例高于野生型FLT3（FLT3－wt）组。FLT3－ITD阳性组患者完全缓解（CR）率47．6％，显著低于FLT3－wt88．1％（P〈0．05）。20例M3患者中，FLT3－ITD阳性组及阴性组患者缓解率差异无统计学意义；非M3FLT3－ITD阳性组患者cR率为37．5（6／16例），显著低于非M3FLT3－wt组患者CR率90．6％（48／53例）（P〈0．05）。阳性组患者完全缓解后14个月（2—20个月）内复发3例，复发率为50％（3／6），高于FLT3－wt组29．2％（14／48例）。由于FLT3－TKD阳性患者仅3例，未单独进行统计学分析。结论：FLT3基因突变是AML患者中常见的突变，FLT3－ITD突变较FLT3－TKD点突变发生率高，FLT3－ITD有突变的AML患者预后差；FLT3－TKD点突变对预后的影响不明显。临床上早期FLT3基因突变检测对AML患者今后的靶向治疗及了解临床预后有重要意义。

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 manonuclear cells was detected by genomic DNA-PCR, the TKD point mutation in FLT3 exon 20 was detected by genomic DNA-PCR combined with restriction endonuclear 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 M3 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 relaapsed after CR for 14 （2 -20） months with ralapse 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 mntation may be inportant for targeting therapy and evaluating clinical prognosis of AML patients.