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Chronic myleproliferative neoplasms

Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression

Leukemia volume 30, pages 124–130 (2016)Cite this article

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Abstract

Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1β, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1β, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients—66 indolent SM (ISM) and 9 aggressive SM—and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1β, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high-risk ISM patients who carry multilineage KIT mutation.

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Acknowledgements

This work was supported by Fondo de Investigaciones Sanitarias (FIS) of the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain (grant PI11/02399, FEDER), and Fundacion Ramon Areces, Madrid, Spain (grant CIVP16A1806). AM and AR-C were supported by a grant RTICC (Red Tematica de Investigacion Cooperativa en Cancer, grant RD12/0036/0048, FIS, FEDER). SM was supported by Fundación Científica de la Asociación Española contra el Cáncer. We gratefully acknowledge Juan Alejandro Flores Montero for his contribution in the recruitment of the controls.

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Authors and Affiliations

  1. Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Servicio General de Citometría (NUCLEUS), Universidad de Salamanca, Salamanca, Spain

    A Mayado, A C Garcia-Montero, A Rodriguez-Caballero, C Muñiz, M Jara-Acevedo, S Matarraz, C Caldas, J I Muñoz-González, L Escribano & A Orfao

  2. Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

    C Teodosio

  3. Centro de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain

    A Matito, J M Morgado, I Álvarez-Twose & L Sanchez-Muñoz

  4. Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF) Instituto de Salud Carlos III, Madrid, Spain

    C Muñiz

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  1. A Mayado
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Correspondence to A Orfao.

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Mayado, A., Teodosio, C., Garcia-Montero, A. et al. Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression. Leukemia 30, 124–130 (2016). https://doi.org/10.1038/leu.2015.176

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