| 急性髓系白血病干细胞免疫表型和信号通路蛋白活化检测及意义 |
| 投稿时间：2011-03-24 修订日期：2011-09-09 点此下载全文 |
| 引用本文：郑瑞,陈葆国,干灵红,章卫国.急性髓系白血病干细胞免疫表型和信号通路蛋白活化检测及意义[J].医学研究杂志,2011,40(11):89-93 |
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| 基金项目:台州市“211人才工程”基金资助项目［台人专(2009)236号］ |
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| 中文摘要: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7209％，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＜001）。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。 |
| 中文关键词:急性髓系白血病 白血病干细胞 免疫表型 p-Akt p-ERK |
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| Clinical Significance of the Immunophenotype and Signal Transduction Protein in Acute Myeloid Leukemia Leukemic Stem Cells |
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| Abstract:ObjectiveTo investigate the characteristics of the immunophenotype and the status of signal transduction proteins in acute myeloid leukemia leukemic stem cells (AML-LSCs). MethodsImmunophenotype 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. ResultsThe 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 (2558%) 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). ConclusionThe 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. |
| keywords:Acute myeloid leukemia Leukemic stem cells Immunophenotype p-Akt p-ERK |
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