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Chronic Myeloproliferative Disorders

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

Leukemia volume 22, pages 1368–1376 (2008)Cite this article

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.

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Acknowledgements

This work was supported by grants FIS PI030345 and PI071009 from the Spanish Ministry of Health and Beca de Investigación FEHH. We thank Manuel Delgado, Norma Carmen Gutiérrez and Jesús Ma Hernández-Rivas from Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer (CIC), for their help in microarray data analyses and Josep M Manresa from Assessorament Metodològic en Investigació Biomèdica (AMIB) Department, IMIM-Hospital del Mar, for the statistical analysis of the clinical data.

Authorship contribution: EP processed the samples, carried out the microarray study and real-time quantitative RT-PCR analysis, and wrote the manuscript; BE designed the study and wrote the paper; JJL, LS performed the statistical analysis of the microarray and the real-time quantitative RT-PCR data; BB carried out the JAK2 analysis and provided molecular biology laboratory support; LA provided basic laboratory support; AA and CB collected the patients data; FS performed cytogenetics studies; SS was head of the laboratory that was involved in the biology studies; LF designed the study and wrote the paper. All authors reviewed and accepted the manuscript.

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Authors and Affiliations

  1. Laboratori de Citogenètica i Biologia Molecular, Servei de Patologia. Hospital del Mar, IMAS, Barcelona, Spain

    E Puigdecanet, B Espinet, B Bellosillo, F Solé & S Serrano

  2. Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, IMAS, Barcelona, Spain

    E Puigdecanet, L Arenillas, S Serrano & L Florensa

  3. GRETNHE, IMIM-Hospital del Mar, Barcelona, Spain

    E Puigdecanet, B Espinet, L Arenillas, F Solé, S Serrano & L Florensa

  4. Departament de Biologia Cellular, Fisiologia i Immunologia. Facultat de Biociències. Universitat Autònoma de Barcelona, Bellaterra, Spain

    E Puigdecanet

  5. Escola de Citologia Hematològica Soledad Woessner-IMAS, Barcelona, Spain

    B Espinet, L Arenillas, F Solé & L Florensa

  6. Laboratori de Microarrays, Programa de Bioinformàtica i Genòmica, Centre de Regulació Genòmica-UPF, Barcelona, Spain

    J J Lozano & L Sumoy

  7. Plataforma de Bioinformática, CIBERehd, Hospital Clinic, Barcelona, Spain

    J J Lozano

  8. Servei d’Hematologia Clínica, Hospital del Mar, IMAS, Barcelona, Spain

    A Álvarez-Larrán & C Besses

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  1. E Puigdecanet
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Correspondence to L Florensa.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Puigdecanet, E., Espinet, B., Lozano, J. et al. Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia. Leukemia 22, 1368–1376 (2008). https://doi.org/10.1038/leu.2008.112

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