摘要
目的研究成人急性白血病(AL)患者FMS样酪氨酸激酶3(FLT3)及核仁磷酸蛋白(NPM1)基因突变发生情况及临床意义。方法采用PCR结合DNA测序技术分析65例初诊急性白血病(AL)患者骨髓单个核细胞中FLT3及NPM1基因突变发生情况。结果在59例急性髓系白血病(AML)患者中检测到FLT3-ITD突变阳性10例(16.9%),NPM1突变阳性15例(25.4%),其中3例同时存在FLT3-ITD突变及NPM1基因突变;而在6例急性淋巴细胞白血病(ALL)患者中均未检测到FLT3-ITD突变或NPM1基因突变。两种突变均与初诊时中位WBC数、染色体正常核型比例及伴有特异性融合基因患者比例有相关关系(P<0.05)。FLT3-ITD+AML患者初诊时骨髓原始细胞比例高(P<0.05),单纯NPM1+AML患者初诊时表现为BPC较高(P<0.05)、免疫表型CD34阳性患者比例低(P<0.05);FLT3-ITD突变阳性者化疗后有低缓解率趋势。结论 FLT3-ITD突变和NPM1基因突变是AML患者常见的基因突变类型。对初诊时高白细胞计数、血小板计数不低、骨髓原始细胞比例高、CD34阴性表型和正常核型的AML患者检测FLT3-ITD突变和NPM1突变,有利于临床判断预后和指导治疗。
Objective To investigate the FLT3 and NPM1 gene mutations in adult acute leukemia and its clinical significance.Methods PCR and DNA sequencing were used to detect the FLT3 and NPM1 gene mutations in blast cells of bone marrow from 65 adult patients with newly diagnosed acute leukemia（AL）.Results 59 acute myeloid leukemia（AML） samples were analyzed,there 10 cases（16.9%） were FLT3-ITD positive,and 15 cases（25.4%） were NPM1 positive.Among these patients with FLT3 or NPM1 mutations,and three were both FLT3-ITD and NPM1 mutations.No FLT3-ITD or NPM1 mutation was found in 6 cases of ALL.Median WBC counts,incidence of normal karyotypes or cases with fusion gene were correlated with FLT3-ITD or NPM1 mutation（P 0.05）.FLT3-ITD mutation was related to high percentage of bone marrow blast cells（P 0.05）.Compared with FLT3-ITD-/ NPM1 AML patients,FLT3-ITD-/ NPM1 ＋ AML patients were associated with higher BPC count（P 0.05） and lower incidence of CD34 positive（P 0.05）.FLT3-ITD mutation was associated with lower complete remission rate.Conclusion FLT3-ITD and NPM1 gene mutations are the prevalent mutations in patients with AML.It is necessary to detect FLT3-ITD and NPM1 mutation in newly diagnosed AML patients,especially in patients with high WBC and BPC,higher percentage of bone marrow blast cells,CD34-negative and normal karyotype,which might help to prognosis and treatment.
出处
《宁夏医学杂志》
CAS
2013年第7期589-592,I0001,共5页
Ningxia Medical Journal
基金
宁夏科技厅科技攻关项目(201125)
