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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-07

AUTHORS

E Puigdecanet, B Espinet, J J Lozano, L Sumoy, B Bellosillo, L Arenillas, A Álvarez-Larrán, F Solé, S Serrano, C Besses, L Florensa

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. More... »

PAGES

leu2008112

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2008.112

DOI

http://dx.doi.org/10.1038/leu.2008.112

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000082142

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18480837


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298 schema:name GRETNHE, IMIM-Hospital del Mar, Barcelona, Spain
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309 schema:name Laboratori de Microarrays, Programa de Bioinformàtica i Genòmica, Centre de Regulació Genòmica-UPF, Barcelona, Spain
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312 schema:name Departament de Biologia Cellular, Fisiologia i Immunologia. Facultat de Biociències. Universitat Autònoma de Barcelona, Bellaterra, Spain
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314 Laboratori de Citogenètica i Biologia Molecular, Servei de Patologia. Hospital del Mar, IMAS, Barcelona, Spain
315 Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, IMAS, Barcelona, Spain
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