title: 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.
abstract: 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.
authors.affiliation: Centro de Investigación del Cáncer, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Andres C
authors.initials: AC
authors.lastname: Garcia-Montero
authors.forename: Maria
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodosio
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Sanchez
authors.forename: Rosa
authors.initials: R
authors.lastname: Nunez
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Prados
authors.forename: Isabel
authors.initials: I
authors.lastname: Aldanondo
authors.forename: Laura
authors.initials: L
authors.lastname: Sanchez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Dominguez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
authors.forename: Francisca
authors.initials: F
authors.lastname: Sanchez-Jimenez
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Luis
authors.initials: L
authors.lastname: Escribano
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism*; D019070:Cell Lineage; D002648:Child; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008415:Mastocytosis / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013030:Spain
chemical_list: D019009:Proto-Oncogene Proteins c-kit