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目的确定高嗜酸性粒细胞综合征(HES)是否存在Janus酪氨酸激酶/信号传导与转录激活因子(JAK/STAT)信号途径的激活;进一步揭示HES的发病机制,并动态观察1例HES患者对甲磺酸伊马替尼(格列卫)治疗的临床反应及JAK/STAT蛋白质和FIP1L1 PDGFRA融合基因的变化。方法用Western印迹技术检测4例HES患者(3例FIP1L1 PDGRA阳性, 1例阴性),患者粒细胞中JAK2、STAT3及磷酸化STAT5(P STAT5)蛋白质表达水平;对1例FIP1L1 PDGFRA融合基因阳性的HES患者口服小剂量格列卫治疗,用逆转录(RT) 筑巢聚合酶链反应(PCR)及Western印迹技术动态检测格列卫治疗前、治疗后10、30、60d患者粒细胞的FIP1L1 PDGFRA融合基因及JAK2、STAT3、STAT5及P STAT5的表达。结果FIP1L1 PDGFRA融合基因阳性的3例HES患者均有JAK2,STAT3及P STAT5蛋白质表达的显著上调;而1例FIP1L1 PDGFRA阴性的HES患者上述蛋白表达几乎阴性。其中1例FIP1L1 PDGFRA( +)的HES患者服用小剂量格列卫治疗后,达到持续性血液学缓解(血象及嗜酸性粒细胞比例恢复正常,症状体征消失);服药30d后FIP1L1 PDGFRA融合基因的表达量明显减低, 60d后融合基因表达阴性;JAK2、STAT3、STAT5及P STAT5蛋白质表达呈时间依赖性下调, 60d后表达均阴性。结论HES患者粒细胞存在JAK/STAT信号途径的过?
OBJECTIVE: To determine whether Janus tyrosine kinase / signal transducer and activator of transcription (JAK / STAT) signaling pathway is activated in hypereosinophilic syndrome (HES). To further elucidate the pathogenesis of HES, Clinical response to imatinib mesylate (Gleevec) treatment and changes in JAK / STAT protein and FIP1L1 PDGFRA fusion gene. Methods Western blotting was used to detect the protein expression of JAK2, STAT3 and P STAT5 in 4 HES patients (3 cases of FIP1L1 PDGRA positive and 1 negative), and 1 case of FIP1L1 PDGFRA fusion gene was positive HES patients were treated with low dose of Gleevec. The levels of FIP1L1 and PDGFRA in granulocytes of 10, 30 and 60 days after treatment with Gleevec were detected by reverse transcription (RT) nested polymerase chain reaction (PCR) and Western blotting Fusion gene and the expression of JAK2, STAT3, STAT5 and P STAT5. Results The protein expression of JAK2, STAT3 and P STAT5 in three HES patients with FIP1L1 PDGFRA fusion gene was significantly up-regulated. The expression of one of the three HES patients with negative FIP1L1 PDGFRA gene expression was almost negative. One case of FIP1L1 PDGFRA (+) HES patients after taking low-dose Gleevec treatment, sustained hematological relief (blood and eosinophil ratio returned to normal, the symptoms and signs disappeared); 30 d after taking FIP1L1 PDGFRA fusion gene The expression of JAK2, STAT3, STAT5 and P STAT5 was down-regulated in 60 days, but negative in 60 days. Conclusions There is JAK / STAT signal pathway in granulocytes of HES patients.