Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia
Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia
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DOI：
10.1038/leu.2008.112
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发表时间：
2008-07-01
期刊：
影响因子：
11.4
通讯作者：
Florensa, L.
中科院分区：
文献类型：
--
作者：
Puigdecanet, E.;Espinet, B.;Florensa, L.
为了探索原发性血小板增多症（ET）患者中与JAK 2 V617 F突变状态相关的基因表达特征，在循环粒细胞中进行表达谱分析。20 ET研究了芯片分析和结果证实了40 ET患者，没有接受细胞减灭治疗的实时定量RT-PCR。一个异质性的分子特征，其特征在于两个主要的基因表达模式被发现：一个与中性粒细胞活化和血栓形成相关的炎症基因的上调，和其他这些基因的表达显着降低。监督聚类分析显示30个基因在JAK 2 V617 F阴性和JAK 2 V617 F阳性ET患者中差异表达。在JAK 2 V617 F阴性中，一组14个基因（CISH、C13 orf 18、CCL 3、PIM 1、MAFF、SOCS 3、ID 2、GADD 45 B、KLF 5、TNF、LAMB 3、HRH 4、TAGAP和TRIB 1）显示异常表达模式。在这组患者中，参与JAK-STAT信号通路的CISH、SOCS 2、SOCS 3和PIM 1基因表达较低。建立了一个包含FOSB和CISH基因的双基因预测模型，这两个基因是JAK 2 V617 F状态的最佳判别器。总之，JAK 2 V617 F阴性ET患者呈现出不同于JAK 2 V617 F阳性患者的特征性基因表达谱。除JAKSTAT外，其他途径可能与JAK 2 V617 F阴性ET患者的病理生理学有关。
To explore the gene expression signature in essential thrombocythemia ( ET) patients in relation to JAK2V617F mutational status, expression profiling in circulating granulocytes was performed. Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients, not receiving cytoreductive treatment. A heterogeneous molecular signature characterized by two main gene expression patterns was found: one with an upregulation of inflammatory genes related to neutrophil activation and thrombosis, and the other with significantly lower expression of these genes. Supervised clustering analysis showed 30 genes differentially expressed between JAK2V617F-negative and JAK2V617F-positive ET patients. Among the JAK2V617F-negative, a set of 14 genes (CISH, C13orf18, CCL3, PIM1, MAFF, SOCS3, ID2, GADD45B, KLF5, TNF, LAMB3, HRH4, TAGAP and TRIB1) showed an abnormal expression pattern. In this group of patients, CISH, SOCS2, SOCS3 and PIM1 genes, all involved in JAK-STAT signalling pathway, presented a lower expression. A two-gene predictor model was built comprising FOSB and CISH genes, which were the best discriminators of JAK2V617F status. In conclusion, JAK2V617F-negative ET patients present a characteristic gene expression profile, different from JAK2V617F-positive patients. Other pathways, besides JAKSTAT, might be implicated in the pathophysiology of JAK2V617F-negative ET patients.