FLT3-ITD gene mutation and its prognostic significance in patients with acute myeloid leukemia
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摘要: 目的:分析急性髓细胞白血病(AML)患者中fms样酪氨酸激酶3(FLT3)基因的内部串联重复(internal tandem duplication,ITD)突变的发生率,以及该突变对患者的血常规水平、免疫表型、完全缓解(CR)率和总生存时间的影响。探讨FLT3 ITD(+)AML患者服用索拉菲尼对中位生存时间的影响。方法:采用PCR方法检测130例初诊急性髓细胞白血病患者骨髓中FLT3-ITD的表达,用Kaplan-Meier生存曲线分析AML的预后。结果:130例初发AML患者中检出FLT3-ITD(+)患者共23例(17.7%)。FLT3-ITD(+)患者发病时白细胞高、骨髓原始细胞比例高(P<0.05),FLT3-ITD(+)对AML(除外APL)患者的CR率、OS时间均有不良影响(P<0.05)。索拉菲尼联合化疗的FLT3-ITD(+)患者的中位生存时间有所延长(12个月,未口服则为7个月)。结论:FLT3-ITD突变是AML患者中常见的基因突变类型,FLT3-ITD(+)降低患者的CR率,缩短OS。索拉菲尼可作为FLT3-ITD(+)急性髓细胞白血病患者的治疗选择。Abstract: Objective:To analyze the prevalence of internal tandem duplication mutations in the FMS like tyrosine 3 (FLT3 ITD) in acute myeloid leukemia,and the mutation's influence on the blood cell counts,immunophenotype,complete remission (CR) rate and overall survival(OS) time.To investigate the median survival time of FLT3 ITD (+) patients with sorafenib.Method:The mutation of FLT3 ITD in bone sameples from 130 patients with de novo AML were screened by polymerase chain reaction(PCR),analyze the prognosis of AML by Kaplan-Meier survival curve.Result:FLT3-ITD(+) were found in 23(17.7%) of 130 de novo AML patients,and was associated with higher white cell count(P<0.05) and higher percentage of bone marrow blast cells(P<0.05).FLT3-ITD(+)have lower CR rate and OS time than the negative.The median survival time is lengthened from 7 months to 12 months for the FLT3-ITD(+) patients taking sorafenib.Conclusion:FLT3-ITD mutations is a common genetic abnormality in AML patients and associated with low CR rate and short overall survival.Sorafenib show activity in FLT-ITD(+) AML patients.
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Key words:
- acute myeloid leukemia /
- FLT3-ITD /
- gene mutation /
- sorafenib
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