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FLT3基因表达在急性髓系白血病中的临床意义

FLT3 Gene Expression and Its Clinical Significance in Acute Myeloid Leukemia

  • 摘要: 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。

     

    Abstract: Objective To determine the correlation between fms-like tyrosine kinase 3 gene (FLT3) expression and FLT3-internal tandem duplication (ITD) mutations in acute myeloid leukemia patients, and the association between expression of FLT3 gene and clinical and laboratory features of patients. Methods The expression of FLT3 mRNA in bone marrow (BM) leukemic cells of 128 acute myeloid leukemia (AML) patients was measured by real-time PCR. The patients were divided into two groups using the 35% FLT3 expression as a cut-off point. The associations between the expression level of FLT3 and clinical and laboratory features of patients were analyzed. Results The patients had a FLT3 gene expression level of 0.01-180.68 (mean 14.65) at the initial diagnosis, with AML-M1 the most expressed and AML-M6 the least expressed, but without statistical significance. The patients with a high level of FLT3 gene expression had higher peripheral blood white blood cell count (WBC) (P<0.01) and were more likely to become anemic and febrile (P<0.05). WBC 〔regression coefficient (B)=1.508,odds ratio (OR)=4.518,95% confidence interval(CI):1.465-13.390,P=0.009〕 and anemia (B=2.142,OR=8.513,95%CI:3.201-22.644,P<0.001)were predictors of higher expression of FLT3. The patients with high levels of FLT3 gene expression had lower complete remission rate (32/83), compared with those (36/44) with low levels of FLT3 gene expression (P<0.05). The Cox regression analysis showed that the patients with higher levels of FLT3 gene expression had a higher risk of death (B=1.338,relative risk=3.810,95%CI:1.820-7.947,P<0.001). The Kaplan-Meier analysis showed that the patients with higher levels of FLT3 gene expression had lower survival time (56.63%) than those with lower levels of FLT3 expression (70.45%, P<0.05). Conclusion FLT3 gene has adverse impacts on complete remission of AML. High expression of FLT3 gene is associated with poor prognosis of patients with AML.

     

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