骨髓增生异常综合征表皮生长因子受体的表达及其与细胞凋亡的关系

目的　探索骨髓增生异常综合征 (MDS)造血细胞中表皮生长因子受体 (EGFR)表达及其与细胞凋亡的关系。方法　取 18例MDS患者骨髓有核细胞经离心涂片机制片 ,用免疫酶标记方法(碱性磷酸酶 抗碱性磷酸酶系统 ,APAAP)及TdT介导的dUTP缺口末端 (荧光素 )标记 (TUNEL)法先后在同一标本上检测EGFR表达和凋亡信号。 9名正常人骨髓作对照。另外 ,18例MDS中有 15例、9名正常人中有 6名经流式细胞仪分选CD3 4+细胞并制备涂片后按上述方法进行EGFR和凋亡检测 ,并分析两者间的关系。结果　①MDS骨髓细胞EGFR表达 [(38.6± 2 4.6 ) %]高于正常对照 [(18.1±14 0 ) %](P <0 .0 5 ) ;②MDS细胞凋亡主要发生在EGFR阴性细胞 (16 .1%) ,EGFR阳性细胞中凋亡细胞仅占 1.4%(P <0 .0 1) ,EGFR表达与细胞凋亡呈负相关 (r =- 0 .70 1;tr=3.6 0 ;P <0 .0 1) ;③CD3 4+细胞EGFR表达阳性率RAEB RAEB t CMML组高于RA RAS组 ,分别为 (2 0 .6± 2 7.9) %和 (8.9±11 8) %,但差异无显著性 ,细胞凋亡率RAEB RAEB t CMML组低于RA RAS组 ,分别为 (18.2± 12 5 ) %和 (4 5 .2± 2 0 .5 ) %(P <0 .0 5 )。结论　MDS造血细胞过度表达EGFR。EGFR表达增高可能预示MDS的恶性增殖倾向并通过某种途径抑制细胞凋亡。因此抗EGFR治疗有希望成为治疗MDS

Expression of epidermal growth factor receptor and its relationship to apoptosis in myelodysplastic syndromes

OBJECTIVE: To explore the expression of epidermal growth factor receptor (EGFR) in hematopoietic cells and investigate its relationship to apoptosis in myelodysplastic syndrome (MDS) patients. METHOD: Mononuclear cells from 18 MDS patients were used to analyze the expression of EGFR and the apoptotic signals by immunocytochemical technique and TdT-mediated dUTP nick end labelling (TUNEL) fluorescein. Flow cytometry (FCM) sorted CD(34)(+) cells from 15 MDS cases and 6 normal donors were also analyzed for the EGFR expression and apoptotic signals. Nine normal marrow samples were taken as controls. EGFR expression and its relationship to apoptosis were analysed. RESULTS: (1) There was a higher EGFR expression rate (38.6 +/- 24.6)% in nucleated cells of MDS marrow than in normal marrow (18.1 +/- 14.0)% (P < 0.05). (2) Apoptosis occurred much more in EGFR negative cells (16.1%) than in EGFR positive cells (1.4%) (P < 0.01). EGFR expression showed negative correlation with apoptosis (r = -0.701; t(r) = 3.60; P < 0.01). (3) In CD(34)(+) cells, EGFR expression rate seemed higher in RAEB/RAEB-t/CMML than that in RA/RAS (20.6 +/- 27.9 vs 8.9 +/- 11.8%) subgroup (P > 0.05), while apoptosis was lower in RAEB/RAEB-t/CMML subgroup than in RA/RAS cases (18.2 +/- 12.5 vs 45.2 +/- 20.5%) (P < 0.05). CONCLUSION: There is overexpression of EGFR in MDS cases. And it seems that the overexpressed EGFR represent somewhat the malignant proliferation in MDS and suppress apoptosis through a unknown mechanism.