title: Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression.
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.
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mayado
authors.affiliation: Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Teodosio
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: A C
authors.initials: AC
authors.lastname: Garcia-Montero
authors.affiliation: Centro de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Matito
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Caballero
authors.affiliation: Centro de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Morgado
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.|Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF) Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Muñiz
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Jara-Acevedo
authors.affiliation: Centro de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Álvarez-Twose
authors.affiliation: Centro de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Sanchez-Muñoz
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Matarraz
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Caldas
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Muñoz-González
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Escribano
authors.affiliation: Servicio General de Citometría (NUCLEUS), Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Orfao
mesh_terms: D019742:Chemokines, CC / Q000097:blood; D018450:Disease Progression; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D034721:Mastocytosis, Systemic / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012306:Risk
chemical_list: C105504:CCL23 protein, human; D019742:Chemokines, CC; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D019009:Proto-Oncogene Proteins c-kit