NPM1和FLT3基因突变的正常核型急性髓系白血病病人临床特征及预后分析

NPM1 AND FLT3 MUTATIONS IN PATIENTS WITH NORMAL KARYOTYPE ACUTE MYELOID LEUKEMIA:CLINICAL CHARACTERISTICS AND PROGNOSIS

目的了解正常核型急性髓系白血病（AML）病人核仁磷酸蛋白1（NPM1）、FMS样酪氨酸激酶3（FLT3）基因突变的发生频率，并探讨基因突变伴随的临床特征及对近期预后的影响。方法收集94例初治的正常核型AML病人（M3除外），行NPM1、FLT3基因突变检测。结果94例正常核型AML病人，NPMl基因突变阳性率为40．43％}FLT3内部串联重复突变（FLT3-ITD）阳性率为28．72％；NPM1并FLT3-ITD基因突变阳性率为14．89％；FLT3点突变（FLT3-TKD）阳性率为7．45％。与无突变组相比，NPM1＋／FLT3组发病年龄、外周血白细胞和血小板计数、骨髓原始细胞比例均较高，差异有显著性（t=2．048～2．072，P〈0．05）。NPM1／FLT3-ITD＋组外周血白细胞计数和骨髓原始细胞比例均较无突变组高（f=2．549、2．784，P〈0．05）。NPM1＋／FLT3～组1疗程化疗诱导完全缓解率为87．50％，高于无突变组的63．89％（χ2=4．205，P〈0．05）；NPM1／FLT3-ITD＋。组完全缓解率为53．85％，与无突变组比较差异无统计学意义（P〉0．05）。结论NPM1、FLT3基因突变是正常核型AML病人中常见的分子学异常，此两种基因突变检测对AML病人的个体化治疗及预后评估有重要意义。

Objective To investigate the frequency of nucleophosmin （NPM1） and FMSqike tyrosine kinase-3 （FLT3） mutation and its effect on clinical features and short-term prognosis in patients with normal karyotype acute myeloid leukemia （AML）. Methods Ninety-four patients who received initial treatment for normal karyotype AML （M3 was excluded） were recruited, and NPM1 and FLT3 mutation detected. Results In f14 normal karyotype AML patients, the mutation rate of NPM1 gene was 40.43%, that of FLT3-ITD gene was 28.72%, coexist FLT3-ITD and NPM1 mutation was 14.89%, and FLT3-TKD mutation rate was 7.45 %. Compared with no-mutation group, the age of onset in patients in NPM1 ＋/FLT3- group was older, the white blood cells, platelet counts and percentage of bone marrow blasts in peripheral blood were higher （t =2.048 2.072,P~ 0.05）. The patients in NPM1-/FLT3 ITD＋ group had higher white blood cell counts and percentage of bone marrow blasts than that in the no-mutation group （t = 2.549,2.784;P 〈0.05）. After one course of chemotherapy-induced treatment, the complete re mission rate was 87.50% in NPMI＋/FLT3- group versus 63.89% in no-mutation group, the difference was significant （χ2=4.205 ,P〈0.05）, and the complete remission rate in NPM1-/FLT3-ITD＋ group was 53.85%, no statistical difference was found as compared with no-mutation group （P〉0.05）. Conclusion NPM1 and FLT3 gene mutation are common in AML patients with normal karyotype, the detection of these two gene mutations is of important significance for individualized therapy and prog- nostic assessment of the disease.