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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2366-2372.
Prepublished online as a Blood First Edition Paper on June 1, 2006; DOI 10.1182/blood-2006-04-015545.
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NEOPLASIA
KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients
Andres C. Garcia-Montero,
Maria Jara-Acevedo,
Cristina Teodosio,
Maria Luz Sanchez,
Rosa Nunez,
Aranzazu Prados,
Isabel Aldanondo,
Laura Sanchez,
Mercedes Dominguez,
Luis M. Botana,
Francisca Sanchez-Jimenez,
Karl Sotlar,
Julia Almeida,
Luis Escribano, and
Alberto Orfao
From the Servicio General de Citometría, Centro de Investigación del Cáncer, and Departamento de Medicina, Universidad de Salamanca, Spain; Unidad de Mastocitosis, Laboratorio K. Frank Austen, Hospital Ramón y Cajal, Madrid, Spain; Servicio de Inmunología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain; Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela (USC), Lugo, Spain; Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain; and the Institute for Pathology, University of Tübingen, Germany.
Despite the relevance of the c-kit/stem cell factor (SCF) signaling pathway in mast cell (MC) diseases, the exact frequency of KIT mutations in different compartments of bone marrow (BM) hematopoietic cells of individuals with systemic mastocytosis (SM), and its different diagnostic categories, remains unknown. In this study, we prospectively analyzed the presence of KIT mutations in fluorescence-activated cell-sorting (FACS)– purified populations of BM MCs (n = 113) and other BM cell compartments (n = 67) from adults with SM. Our results show the presence of D816V KIT mutation in virtually all adults (93%) with indolent and aggressive forms of SM, except well-differentiated SM (29%), while other KIT mutations were rarely (< 3%) detected. In around one-third of patients with mutated MCs, the KIT mutation was also detected in CD34+ hematopoietic cells and eosinophils, and, to a lesser extent, in monocytic, neutrophil-lineage BM precursor cells and lymphocytes. Most patient with poor-prognosis SM (81%) carried the KIT mutation in 2 or more BM myeloid cell populations, while this was detected in a smaller proportion (27%) of indolent cases. These results would support the notion that KIT mutation is a hallmark of adult SM where it targets a pluripotent hematopoietic stem cell, and may contribute to explaining previously observed discrepancies in the literature.
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