急性髓系白血病患者 FLT3基因 ITD、TKD 突变观察及其临床分析

摘要

目的：观察急性髓系白血病（AML）患者Fms样酪氨酸激酶3（FLT3）基因内部串联重复（ITD）突变、酪氨酸激酶结构域（ TKD）点突变的发生情况，分析并比较双突变患者与单突变患者的临床资料。方法 AML患者432例，取新鲜骨髓分离单个核细胞，提取DNA，采用PCR法对FLT3基因第14、15外显子多发突变区及第20外显子突变区进行扩增，经琼脂糖凝胶电泳，分析ITD、TKD突变情况。收集并比较FLT3基因ITD、TKD双突变AML患者与单突变患者的性别、年龄、白细胞、血红蛋白、血小板、外周血原始细胞比例、骨髓原始细胞比例、治疗缓解情况等资料。结果432例AML患者中共检出FLT3基因突变102例。 TKD、ITD双突变11例；FLT3基因单突变91例，其中ITD突变60例，TKD突变31例。 FLT3基因ITD、TKD双突变与单突变患者的性别、年龄、白细胞、血红蛋白、血小板、骨髓原始细胞比例、外周血原始细胞比例及治疗缓解情况差异均无统计学意义。结论少数AML患者可同时发生FLT3基因ITD、TKD突变，FLT3基因双突变患者与单突变患者临床特征无明显差异。%Objective To observe the concurrence of acute myeloid leukemia ( AML) patients with FLT3 mutation-in-ternal tandem duplication ( FLT3-ITD) mutation and point mutation in the tyrosine kinase domain ( FLT3-TKD) , and then to analyze and compare the clinical characteristics between patients with the double mutations and patients with single muta-tion.Methods A total of 432 patients with AML were selected.We obtained the fresh bone marrow to separate the mono-nuclear cells and extract DNA.The amplifications of FLT3 gene exons 14, 15 multiple mutation domains and exon 20 muta-tion domain was conducted by PCR.ITD and TKD mutations were analyzed by agarose gel electrophoresis (AGE).The clinical data of patient′s gender, age, white blood cells, hemoglobin, platelets, primitive cell percentages of peripheral blood and bone marrow, and remission in AML patients with both FLT3-ITD and FLT3-TKD mutations and patients with single mutation were collected and compared.Results Among 432 AML patients, 102 patients with FLT3 mutation were found, and 11 AML patients with concurrence of both FLT3-ITD and FLT3-TKD mutations;and the other 91 AML patients with only one type of FLT3 mutation, including 60 with FLT3-ITD and 31 with FLT3-TKD.There were no significant differ-ences in the gender, age, white blood cells, hemoglobin, platelets, primitive cell percentages of peripheral blood and bone marrow, and complete remission between AML patients with both FLT3-ITD and FLT3-TKD mutations and AML patients with only one mutation.Conclusions There are a few AML patients with both FLT3-ITD and FLT3-TKD mutations.No significant differences are found in the clinical feathers between patients with both types of FLT3 mutations and patients car-rying only one kind of FLT3 mutation.