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目的研究急性髓系白血病(AML)患者骨髓中FMS样酪氨酸激酶3基因(FLT3)表达水平与FLT3基因内部串联重突变(FLT3-ITD突变)、临床表现和疾病预后的相关性及意义。方法采用荧光定量PCR法检测128例AML患者初诊时骨髓标本中FLT3基因表达水平,以FLT3基因表达量<35%作为低表达组,≥35%作为高表达组,并探讨不同FLT3基因表达水平的FLT3-ITD突变、临床症状、实验室检查结果及疾病预后,采用多因素logistic回归分析FLT3基因高表达的影响因素,采用单因素Cox回归和生存曲线进行生存分析。结果剔除1例不合格的M2患者RNA样本,最终纳入127例进行分析。AML患者初诊时FLT3表达量为0.01~180.68(均值14.65)。FLT3基因表达水平在WHO的AML分型中M1最高,M6最低,但各亚型间差异不具有统计学意义。FLT3基因高表达组AML患者外周血白细胞计数(WBC)较低表达组高(P<0.01),且高表达组患者更容易发生贫血及发热临床症状(P<0.05),多因素logistic回归发现,FLT3基因高表达的可能相关因素为WBC〔回归系数(B)=1.508,比值比(OR)=4.518,95%可信区间(95%CI):1.465~13.390,P=0.009〕及贫血(B=2.142,OR=8.513,95%CI:3.201~22.644,P<0.001)。FLT3基因低表达组AML患者完全缓解率(CR)为81.82%(36/44),高于FLT3基因高表达组38.55%(32/83),(P<0.05)。生存曲线显示,FLT3基因高表达组患者生存时间较低表达组短(P<0.05)。Cox回归显示,FLT3基因表达高水平患者死亡风险是FLT3基因表达低水平者的3.810倍(B=1.338,相对危险度3.810,95%CI:1.820~7.947,P<0.001)。高表达组总生存率为56.63%,低表达组为70.45%,两组间差异有统计学意义(P<0.05)。结论 FLT3基因高表达可能与AML患者WBC及贫血症状有关。FLT3基因高表达是AML患者预后不良的指标。
Objective To study the correlation between the expression of FLT3 gene and the FLT3-FLT3-ITD mutation, clinical manifestations and disease prognosis in patients with acute myeloid leukemia (AML). Methods Fluorescence quantitative PCR was used to detect FLT3 gene expression in bone marrow samples from 128 AML patients newly diagnosed. FLT3 gene expression levels were <35% low expression group and> 35% high expression group, and the expression levels of different FLT3 genes FLT3-ITD mutation, clinical symptoms, laboratory test results and disease prognosis. The multivariate logistic regression analysis was used to analyze the influencing factors of FLT3 gene expression. Survival analysis was performed by single-factor Cox regression and survival curves. Results One patient with unqualified M2 patients was excluded from the RNA samples, and 127 patients were finally included in the analysis. FLT3 expression in AML patients was 0.01 ~ 180.68 (mean 14.65). FLT3 gene expression levels in the WHO AML M1 the highest, M6 the lowest, but the differences between the subtypes was not statistically significant. Patients with high FLT3 gene expression in AML patients had higher WBC (P <0.01), and patients with high expression of FLT3 gene were more likely to develop clinical symptoms of anemia and fever (P <0.05). Multivariate logistic regression analysis showed that, The possible related factors for the high expression of FLT3 gene were WBC (regression coefficient = 1.508, OR = 4.518, 95% CI: 1.465-13.390, P = 0.009) and anemia = 2.142, OR = 8.513, 95% CI: 3.201 ~ 22.644, P <0.001). The complete remission rate (CR) was 81.82% (36/44) in FLT3 low expression group and 38.55% (32/83) in FLT3 high expression group (P <0.05). Survival curves showed that patients with high FLT3 gene expression had shorter survival time (P <0.05). Cox regression showed that the risk of death from high FLT3 gene expression was 3.810 times lower than that of FLT3 (B = 1.338, relative risk 3.810, 95% CI 1.820 to 7.947, P <0.001). The overall survival rate was 56.63% in high expression group and 70.45% in low expression group, with significant difference between the two groups (P <0.05). Conclusion The high expression of FLT3 gene may be related to WBC and anemia in AML patients. FLT3 gene overexpression is an indicator of poor prognosis in patients with AML.