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Chronic Myeloproliferative Neoplasias

An immature immunophenotype of bone marrow mast cells predicts for multilineage D816V KIT mutation in systemic mastocytosis

Leukemia volume 26, pages 951–958 (2012)Cite this article

Abstract

D816V KIT mutation of bone marrow (BM) mast cells (MC) is a common feature to systemic mastocytosis (SM) patients. Nevertheless, occurrence of the KIT mutation in BM cell compartments other than MC is associated with progression to more aggressive forms of the disease and poor outcome in indolent SM (ISM). Here, we assessed the potential association between the immunophenotype of MC and multilineage KIT mutation in the BM of SM patients through the investigation of the flow cytometric protein expression profile (PEP) of bone marrow mast cells (BMMC) from 70 control individuals and 206 SM patients, classified according to the WHO (World Health Organization), and the degree of involvement of BM hematopoiesis by the D816V KIT mutation; additionally, we developed a score-based class prediction algorithm for the detection of SM cases with multilineage mutation. Our results show that aberrant expression of CD25 with a FcɛRIlo, FSClo, SSClo and CD45lo immature phenotype of BMMC, in the absence of coexisting normal MC in the BM, was associated with multilineage involvement by the D816V KIT mutation, regardless of the diagnostic subtype of the disease (for example, indolent vs aggressive SM), which supports the utility of the immunophenotype of BMMC as a surrogate marker to screen for multilineage KIT mutation in ISM.

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Acknowledgements

This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS) of the Ministerio de Ciencia e Innovación of Spain (PS09/00032, PI061377, PI11/02399 and RETICS RD06/0020/0035-FEDER); Junta de Comunidades de Castilla La Mancha (FISCAM 2007/36, FISCAM 2008/46 and G-2010-C/002); Junta de Castilla y León (Grant SAN/103/2011, Ayuda al Grupo GR37 de Excelencia de Castilla y León); CT was supported by a grant from the Fundação para a Ciência e Tecnologia (FCT) of Portugal (SFRH/BD/17545/2004) and by a grant from the Fondo de Investigaciones Sanitarias (FIS) of the Ministerio de Ciencia e Innovación of Spain (PI08/90881). MJ-A was supported by a grant from the Programa personal técnico de apoyo a la investigación. Ministerio de Ciencia e Innovación–Universidad de Salamanca, Spain.

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Author notes

  1. C Teodosio and A C García-Montero: These authors have equally contributed to this work and should both be considered as ‘first author’.

  2. L Escribano and A Orfao: These authors have equally contributed to this work and should both be considered as ‘last author’.

Authors and Affiliations

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

    C Teodosio, A C García-Montero, M Jara-Acevedo, J Almeida & A Orfao

  2. Centro de Estudios de Mastocitosis de Castilla La Mancha, Hospital Virgen del Valle, Toledo, Spain

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

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  1. C Teodosio
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  2. A C García-Montero
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  9. L Escribano
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Correspondence to A Orfao.

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Teodosio, C., García-Montero, A., Jara-Acevedo, M. et al. An immature immunophenotype of bone marrow mast cells predicts for multilineage D816V KIT mutation in systemic mastocytosis. Leukemia 26, 951–958 (2012). https://doi.org/10.1038/leu.2011.293

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