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目的探讨急性髓细胞白血病(AML)患者中 NPM1基因与 FLT3基因内部串联重复(ITD)突变的发生率,并了解其临床特征及预后。方法收集86例成人 AML 患者初诊时骨髓单个核细胞,采用基因组 DNA-PCR 方法分别扩增其 NPM1和 FLT3基因,毛细管电泳方法分析 NPM1第12外显子突变,琼脂糖电泳分析 FLT3-ITD 突变,随访判断其预后。结果 86例 AML 患者中共检出NPM1基因突变29例(33.7%),FLT3-ITD 突变15例(17.4%)。两种突变在50例染色体正常核型AML 中的发生率分别为46.0%和24.0%,明显高于异常核型 AML 患者。7例中6例 NPM1~+/FLT3-ITD~+双阳性 AML 患者表现为正常核型,外周血白细胞均>50×10~9/L。单纯 NPM1~+或 FLT3-ITD~+AML 患者初诊时也表现为高白细胞(P<0.05),NPM1~+AML 患者 CD_(34)表达率较低(P<0.001)、临床完全缓解(CR)率略高(66.7%、53.3%,P>0.05)、总生存率(OS)高(P>0.05);而 FLT3-ITD~+AML患者 CR 率略低(50.0%、58.8%,P>0.05)、OS 低(P>0.05)。NPM1~+/FLT3-ITD~-、NPM1~-/FLT3-ITD~-、NPM1~+/FLT3-ITD~+、NPM1~-/FLT3-ITD~+四组患者的 CR 率分别为66.7%、62.5%、50.0%、42.9%(P>0.05),各组间 OS 差异无统计学意义(P>0.05)。结论 NPM1和 FLT3-ITD 突变是 AML(尤其正常核型 AML)患者常见的分子学异常,且与其临床特点、疗效及预后有一定相关性。
Objective To investigate the incidence of mutations in the NPM1 gene and FLT3 gene in patients with acute myeloid leukemia (AML) and to find out its clinical characteristics and prognosis. Methods The bone marrow mononuclear cells of 86 adult AML patients were collected. The NPM1 and FLT3 genes were amplified by genomic DNA-PCR, the exon 12 of NPM1 was analyzed by capillary electrophoresis, the FLT3-ITD mutation was analyzed by agarose gel electrophoresis, Follow-up to determine its prognosis. Results A total of 86 AML patients were detected in NPM1 gene mutations in 29 cases (33.7%), FLT3-ITD mutations in 15 cases (17.4%). The incidence of two mutations in 50 cases of chromosomal normal karyotype AML were 46.0% and 24.0%, significantly higher than the abnormal karyotype AML patients. Six cases of NPM1 ~ + / FLT3-ITD ~ + double positive AML patients showed normal karyotype and peripheral blood leukocytes> 50 × 10 ~ 9 / L in 7 cases. Patients with NPM1 ~ + or FLT3-ITD ~ + AML showed high white blood cell count (P <0.05) at the first visit, while the expression of CD34 in NPM1 ~ + AML patients was lower (P <0.001) The overall survival rate (OS) was significantly higher in patients with FLT3-ITD ~ + AML (50.0% vs 58.8%, P> 0.05) ), OS low (P> 0.05). The CR rates of NPM1 ~ + / FLT3-ITD ~ -, NPM1 ~ - / FLT3-ITD ~ -, NPM1 ~ + / FLT3- ITD ~ + and NPM1 ~ - / FLT3-ITD ~ + groups were 66.7% 62.5%, 50.0% and 42.9% respectively (P> 0.05). There was no significant difference in OS among the groups (P> 0.05). Conclusions NPM1 and FLT3-ITD mutations are common molecular abnormalities in AML patients, especially in patients with normal karyotype AML, and have certain correlation with clinical features, curative effect and prognosis.