title: Gene expression profile of highly purified bone marrow mast cells in systemic mastocytosis.
abstract: BACKGROUND
  Despite the fact that a great majority (>90%) of patients with systemic mastocytosis (SM) carry a common genetic lesion, the D816V KIT mutation, little is known regarding the molecular and biological pathways underlying the clinical heterogeneity of the disease.
  
  
  OBJECTIVE
  We sought to analyze the gene expression profile (GEP) of bone marrow mast cells (BMMCs) in patients with SM and its association with distinct clinical variants of the disease.
  
  
  METHODS
  GEP analyses were performed by using DNA-oligonucleotide microarrays in highly purified BMMCs from patients with SM carrying the D816V KIT mutation (n=26) classified according to the diagnostic subtype of SM versus normal/reactive BMMCs (n=7). Validation of GEP results was performed with flow cytometry in the same set of samples and in an independent cohort of 176 subjects.
  
  
  RESULTS
  Overall, 758 transcripts were significantly deregulated in patients with SM, with a common GEP (n=398 genes) for all subvariants of SM analyzed. These were characterized by upregulation of genes involved in the innate and inflammatory immune response, including interferon-induced genes and genes involved in cellular responses to viral antigens, together with complement inhibitory molecules and genes involved in lipid metabolism and protein processing. Interestingly, aggressive SM additionally showed deregulation of apoptosis and cell cycle-related genes, whereas patients with indolent SM displayed increased expression of adhesion-related molecules.
  
  
  CONCLUSIONS
  BMMCs from patients with different clinical subtypes of SM display distinct GEPs, which might reflect new targetable pathways involved in the pathogenesis of the disease.
authors: Servicio General de Citometría, Centro de Investigación del Cáncer (IBMCC-CSIC/USAL and IBSAL) and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors: Cristina
authors: C
authors: Teodosio
authors: Andrés C
authors: AC
authors: García-Montero
authors: María
authors: M
authors: Jara-Acevedo
authors: Laura
authors: L
authors: Sánchez-Muñoz
authors: Carlos E
authors: CE
authors: Pedreira
authors: Ivan
authors: I
authors: Álvarez-Twose
authors: Sergio
authors: S
authors: Matarraz
authors: José M
authors: JM
authors: Morgado
authors: Paloma
authors: P
authors: Bárcena
authors: Almudena
authors: A
authors: Matito
authors: Andrea
authors: A
authors: Mayado
authors: Maria Luz
authors: ML
authors: Sanchez
authors: María
authors: M
authors: Diez-Campelo
authors: Luis
authors: L
authors: Escribano
authors: Alberto
authors: A
authors: Orfao
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D018740:Genetic Heterogeneity; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D056724:Immunity, Humoral / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit