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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [array]

ABSTRACT: Using gene expression analysis in combination with genome-wide methylation profiling, we discovered a unique signature pattern that is consistent across the essential thrombocythaemia population regardless of mutation status.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156546 | GEO | 2021/03/02

REPOSITORIES: GEO

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Project description:In order 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 up-regulation of inflammatory genes related to neutrophil activation and thrombosis, and the other one 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 signaling 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. Experiment Overall Design: Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients. Microarray expression profiles were obtained using Whole Human Genome oligonucleotide microarrays (G4112A, Agilent Technologies, Palo Alto, CA). In each microarray experiment, RNA obtained from granulocytes from a single ET patient was compared with a pool of granulocyte RNAs from 10 healthy individuals. Duplicate hybridizations were performed for each comparison with dye-swapping to control.

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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [array]

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