468例急性白血病患者FLT3基因突变及其预后价值分析

FLT3 gene mutation and its prognostic implication in patients with acute leukemia Sino-US Shanghai Leukemia

目的了解以WHO分型诊断的上海地区急性白血病（AL）患者中fms样酪氨酸激酶-3（FLT3）基因突变的发生率，以及其对AL的完全缓解（CR）率、无病生存（DFS）时间和总体生存（OS）时间等预后的影响。方法采用PCR方法检测468例AL患者初诊时FLT3基因内部串联复制（ITD）突变和D835点突变；随访病例，用Kaplan—Meier和Log—rank等生存率分析方法分析AL患者的预后。结果468例AL患者中急性髓系白血病（AML）374例（79．9％），其中FLT3-ITD突变59例（15．9％），FLT3-D835点突变15例（4．0％）；急性淋巴细胞白血病（ALL）83例（17．7％），ALL中未检测到FLT3-ITD突变，检出FLT3-D835点突变2例（2．4％）。FLT3-ITD突变对AML[去除急性早幼粒细胞白血病（APL）]患者的CR率、DFS和OS时间均有不良影响，FLT3-ITD突变阳性和阴性组CR率分别为52．3％和71．2％，中位生存时间分别为9个月和18个月。FLT3-ITD突变对APL的CR率无明显影响，但对DFS和0S时间有不良影响。FLT3-D835点突变对AML患者的预后无明显影响。结论FLT3基因突变在AML中较常发生，其中FLT3-ITD突变对于AML的CR率及OS时间均有明显影响；而FLT3-D835点突变预后意义不大。

Objective To evaluate the prevalence of FLT3 mutation in different subtypes of acute leukemia （AL） patients diagnosed by WHO criteria and its significance in prognosis. Methods Polymerase chain reaction （PCR） was used to detect internal tandem duplication of FLT3 gene （FLT3-ITD） and D835 mutation in 468 firstly diagnosed AL patients and analyzed their prognosis by Kaplan-Meier and log-rank test. Results In 468 AL patients, there were 374 acute myeloid leukemia （AML） cases（79.9% ） and 83 acute lymphoblastic leukemia （ALL）cases（ 17.7% ）. In AM L patients, FLT3-ITD mutation was present in 59 cases（ 15.9% ） while D835 mutation in 15 cases（4.0% ）; and in ALL patients, none for FLT3-ITD while D835 mutation in 2 cases（2.4% ）. FLT3-ITD mutation might adversely affect clinical outcome in AML patients （excluding APL） with a lower CR rate （52.3% vs 71.2% ） and a shorter median survival （9 months vs 18 months）. For APL FLT3-ITD mutation had no effect on CR rate, but with a shorter DFS and OS. There was no evidence that FLT3-D835 affected the prognosis. Conclusion FLT3 mutation is more frequently present in AML and FLT3-ITD is associated with lower CR rate and shorter median survival time while FLT3-D835 has no such effect.