Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia

被引:29
作者
Puigdecanet, E. [1 ,2 ,3 ,4 ]
Espinet, B. [2 ,3 ,5 ]
Lozano, J. J. [6 ,7 ]
Sumoy, L. [6 ]
Bellosillo, B. [2 ]
Arenillas, L. [1 ,3 ,5 ]
Alvarez-Larran, A. [8 ]
Sole, F. [2 ,3 ,5 ]
Serrano, S. [1 ,2 ,3 ]
Besses, C. [8 ]
Florensa, L. [1 ,3 ,5 ]
机构
[1] Hosp del Mar, GRETNHE, Serv Patol, Lab Citol Hematol,IMAS, Barcelona 08003, Spain
[2] Hosp del Mar, IMAS, Serv Patol, Lab Citogenet & Biol Mol, Barcelona 08003, Spain
[3] Hosp del Mar, IMIM, GRETNHE, Barcelona 08003, Spain
[4] Univ Autonoma Barcelona, Fac Biociencies, Dept Biol Cellular Fisiol & Immunol, Bellaterra, Spain
[5] Escola Citol Hematol Soledad Woessner IMAS, Barcelona, Spain
[6] UPF, Ctr Regulacio Genom, Lab Microarrays, Programa Bioinformat & Genom, Barcelona, Spain
[7] Hosp Clin Barcelona, CIBERehd, Barcelona, Spain
[8] Hosp del Mar, IMAS, Serv Hematol Clin, Barcelona, Spain
关键词
essential thrombocythemia; JAK2V617F; gene expression profiling; real-time quantitative RT-PCR;
D O I
10.1038/leu.2008.112
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1368 / 1376
页数:9
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