急性髓细胞白血病NPM1和FLT3-ITD突变检测临床意义分析  

Prevalence of NPM1 and FLT3 gene internal tandem duplication mutations in patients with acute myeloid leukemia and their clinical significance

作　　者：应逸[1] 陈建兰[1,2] 王汉平[1,3] 谢健晋[1] 周薇[1] 陈小卫[1] 陈小燕[1] 

机构地区：[1]广州市第一人民医院血液内科,广东广州510180 [2]南昌市第一人民医院血液内科,江西南昌330008 [3]广东省临床分子医学及分子诊断重点实验室,广东广州510180

出　　处：《中华肿瘤防治杂志》2013年第2期121-124,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:研究核仁磷酸蛋白1(NPM1)FMS样酪氨酸激酶3(FLT3)基因内部串联重复(ITD)突变在急性髓细胞白血病(AML)中发生的情况,并了解其临床特征及预后意义。方法:分别应用高分辨熔解曲线(HRM)和变性高效液相色谱技术(DHPLC)检测103例初诊AML患者NPM1和FLT3-ITD突变情况,并结合临床资料进行分析。结果:103例初诊AML患者中,31例发现NPM1基因突变,20例发现FLT3-ITD突变,阳性率分别为30.1%和19.4%,而在核型正常组中所占的比例分别为47.6%(20/42)和26.2%(11/42)。FLT3-ITD突变型外周血白细胞计数高,t=2.21,P=0.037;骨髓原始细胞比例高,t=2.44,P=0.023;NPM1突变型亦表现为高外周血白细胞计数,t=2.24,P=0.034。在非M3患者中,NPM1突变型的CR与野生型差异无统计学意义,但第1次化疗的CR(76.9%)明显高于野生型患者(35.0%),χ2=12.78,P=0.000 35;FLT3-ITD突变型患者的CR为58.8%,野生型患者为82.6%,两者比较,χ2=4.48,P=0.034;FLT3-ITD突变型患者第1次化疗的CR为17.6%,而野生型患者为55.1%,两者比较,χ2=6.23,P=0.012。31例NPM1基因突变中有6例合并FLT3-ITD突变,NPM1+/FLT3-ITD-组的CR最高(85.0%),1年内RR率最低(17.6%);NPM1-/FLT3-ITD+组的CR最低(54.5%),1年内RR率最高(50.0%)。结论:NPM1和FLT3-ITD突变是AML患者常见的分子遗传学异常,与预后密切相关,可成为目前细胞遗传学预后分组的重要补充,对于指导AML患者的个体化治疗具有重要的临床价值。OBJECTIVE: To evaluate the prevalence of nucleophosmin1(NPM1) and FMS-like tyrosine kinase-3(FLT3) gene internal tandem duplication(FLT3-ITD) mutations in patients with primary acute myeloid leukemia(AML) and to assess their clinical and prognostic significance.METHODS: Using high-resolution melting curve(HRM) and denaturing high performance liquid chromatography(DHPLC) technology NPM1 and FLT3-ITD mutations were detected in 103 patients with primary AML respectively.REULTS: NPM1 and FLT3-ITD mutations were found in 31 cases(30.1%) and 20 cases(19.4%) respectively in 103 patients with primary AML.Moreover,higher mutation percentage was found in AML patients with normal karyotype(47.6% and 26.2%,respectively).FLT3-ITD mutation was significantly associated with higher peripheral white cell(t=2.21,P=0.037) and bone marrow blast cells counts(t=2.44,P=0.023).NPM1 mutation was also significantly associated with higher peripheral white cell count(t=2.24,P=0.034).In primary AML patients excluding APL,there was no difference in CR rate between NPM1 mutation and wild group,but higher CR rate of first induction chemical therapy was achieved in NPM1 mutation group(76.9% vs 35.0%,χ2=12.78,P=0.000 35).Compared with wild group,the total CR rate and the CR rate after first induction chemical therapy was significantly lower in FLT3-ITD mutation group(58.8% vs 82.6%,χ2=4.48,P=0.034;17.6% vs 55.1%,χ2=6.23,P=0.012). According to CR rate and RR within the first year,the NPM1+/FLT3-ITD-group showed a better prognosis(CR 85.0%,RR 17.6%),compared with the other groups.Adversely,the NPM1-/FLT3-ITD+ group was the poorest in prognosis(CR 54.5%,RR 50.0%).CONCLUSIONS: NPM1 and FLT3-ITD mutations are common in patients with primary AML and associated with prognosis.The detection of NPM1 and FLT3-ITD mutations will be beneficial for individual therapy and prognostic assessment in patients with AML.

关 键 词：基因 突变 NPM1 FLT3 内部串联重复 白血病 髓样 急性 

分 类 号：R733.71[医药卫生—肿瘤]