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FLT3ITD(+)AML患...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FLT3ITD(+)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。展开更多
Mutations of fins-like tyrosine kinase 3 （FLT3） and nucleophosmin （NPM1） exon 12 genes are the most common abnormalities in adult acute myeloid leukemia （AML） with normal cytogenetics. To assess the prognostic i...Mutations of fins-like tyrosine kinase 3 （FLT3） and nucleophosmin （NPM1） exon 12 genes are the most common abnormalities in adult acute myeloid leukemia （AML） with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction （PCR） and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication （FLT3/ITD） and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 （19.7%） of 76 subjects, and NPM1 mutation in 20 （26.3%） subjects. Seven （9.2%） cases were positive for both FLT3/ITD and NPM1 mutations Significantly more FLT3/ITD aberration was detected in subjects with French-American-British （FAB） M1 （42.8%）. NPM1 mutation was frequently detected in subjects with M5 （47.1%） and infrequently in subjects with M2 （11.1%）. FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD- positive group had a lower complete remission （CR） rate （53.3% vs. 83.6%）. Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival （OS） and relapse-free survival （RFS）. The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group （P=0.069）. Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.展开更多
文摘目的: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FLT3ITD(+)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。
文摘Mutations of fins-like tyrosine kinase 3 （FLT3） and nucleophosmin （NPM1） exon 12 genes are the most common abnormalities in adult acute myeloid leukemia （AML） with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction （PCR） and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication （FLT3/ITD） and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 （19.7%） of 76 subjects, and NPM1 mutation in 20 （26.3%） subjects. Seven （9.2%） cases were positive for both FLT3/ITD and NPM1 mutations Significantly more FLT3/ITD aberration was detected in subjects with French-American-British （FAB） M1 （42.8%）. NPM1 mutation was frequently detected in subjects with M5 （47.1%） and infrequently in subjects with M2 （11.1%）. FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD- positive group had a lower complete remission （CR） rate （53.3% vs. 83.6%）. Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival （OS） and relapse-free survival （RFS）. The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group （P=0.069）. Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.
