Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia.
Leukemia
; 22(7): 1368-76, 2008 Jul.
Article
in En
| MEDLINE
| ID: mdl-18480837
ABSTRACT
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 JAK-STAT, might be implicated in the pathophysiology of JAK2V617F-negative ET patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Profiling
/
Janus Kinase 2
/
Thrombocythemia, Essential
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Leukemia
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2008
Document type:
Article
Affiliation country:
Spain