【摘要】 目的为了解急性髓系白血病干细胞(AML-LSCs)免疫表型特点和信号转导通路活化状态,以探讨其生物学特征。方法应用流式细胞术检测(AML-LSCs)免疫表型、P-gp、PTEN、p-Akt、p-ERK的表达,以正常造血干细胞(HSCs)为对照。结果正常HSCs主要免疫表型:CD34+、CD38-、CD123-、CD96-、CD117+、CD44+、、CD33-、CD13-。PTEN蛋白阳性率为72.09%,p-Akt及p-ERK蛋白均阴性,P-gp蛋白阴性。AML-LSCs主要免疫表型:CD123+、CD96+、CD117-、CD44+、CD13+、CD33+,与HSCs免疫表型差异主要为CD123+、CD96+、CD117-、CD13+、CD33+。LSCs PTEN蛋白阳性率为25.58%,低于正常HSCs(χ2=30.88,P<0.01),p-Akt阳性率为63.95%,p-ERK阳性率为70.93%,高于正常HSCs(χ2=24.43、30.87,P均<0.01)。P-gp蛋白阳性率为67.44%。79例AML患者预后分析表明,高AML-LSCs的患者较低AML-LSCs患者复发率增高(χ2=5.69,P<0.05);无病生存率(DFS)分析显示,高AML-LSCs的患者无病生存时间中位数14个月,较低AML-LSCs患者无病生存时间中位数28个月明显缩短(P<0.01)。结论 LSCs免疫表型特征为CD34+、CD38-、CD123+、CD96+、CD117-,P-gp高表达。AML-LSCs数量高的AML患者复发率高、无病生存时间短、预后差。MEK/ERK,PI3K/PTEN/Akt信号通路被激活,可能与LSCs克隆性增殖和自我更新有关。更多还原

【Abstract】 Objective To investigate the characteristics of the immunophenotype and the status of signal transduction proteins in acute myeloid leukemia leukemic stem cells(AML-LSCs).Methods Immunophenotype and P-gp,PTEN,p-Akt,p-ERK of the AML-LSCs were analyzed by flow cytometry.Normal hematopoietic stem cells(HSCs) were taken as the normal control.Results The immunophenotype for the HSCs were CD34+,CD38-,CD123-,CD96-,CD117+,CD44+,CD33-and CD13-.72.09% of the HSCs was found to be PTEN positive,while p-Akt,p-ERK and P-gp was absent in HSCs.The major immunophenotype for the AML-LSCs were CD123+,CD96+,CD117-,CD44+,CD13+ and CD33+.Compared to the HSCs,the characteristic phenotype for the AML-LSCs were CD123+,CD96+,CD117-,CD13+ and CD33+.The percentage of PTEN was significantly lower in AML-LSCs(25.58%) than that of the HSCs(χ2=30.8,P<0.01).The expression of p-Akt(64.0%;χ2=24.43,P<0.01) and p-ERK(70.9%;χ2=30.87,P<0.01) was significantly higher in AML-LSCs than in HSCs.Furthermore,P-gp expression was observed in 67.44% patients.Among 79 AML patients,the relapse rate in patients with high AML-LSCs proportions was markedly increased than in those with low AML-LSCs proportions(χ2=5.69,P<0.05),and the dease-free survival(DFS) was significantly decreased in patients with high AML-LSCs percentage than in those with low AML-LSCs percentage(median: 14 months vs 28 months,P<0.01).Conclusion The characteristic immunophenotype for the AML-LSCs were CD34+,CD38-,CD123+,CD96+,CD117-,and P-gp protein positive.Patients with high AML-LSCs percentage were associated with high relapse rate,decreased DSF.Furthermore,the activation of the MEK/ERK,PI3K/PTEN/Akt signal transduction pathway might be involved in the clonal proliferation and self-renewing for the LSCs.更多还原