Gene expression profile of highly purified bone marrow mast cells in systemic mastocytosis - 30/03/13
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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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : Systemic mastocytosis, D816V KIT mutation, gene expression profile, mast cells, cDNA microarrays
Abbreviations used : AHNMD, ASM, BM, BMMC, GEP, ISM, ISMs−, ISMs+, MC, PAM, PI, ROC, SM, SSM, STAT, WHO
Plan
Supported by grants from Fondo de Investigaciones Sanitarias (FIS); PI11/02399; PS09/00032 and RTICC RD06/0020/0035 (FEDER) from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Madrid, Spain); Programa Nacional de Internacionalización de la I+D; PIB2010BZ-00565 from Ministerio de Economía y Competitividad (Madrid, Spain); Junta de Castilla y León (Grant SAN/103/2011); Fundación Sociosanitaria de Castilla-La Mancha (2010/008 y G-2010/C-002); Fundación Española de Mastocitosis (FEM 2010); Brazilian National Research Council (CNPq), and Rio de Janeiro Research Foundation (FAPERJ), Rio de Janeiro, Brazil. C.T. was supported by a grant from Fundação para a Ciência e Tecnologia (FCT) of Portugal (SFRH/BD/17545/2004). M.J.-A. was supported by a grant from Programa personal técnico de apoyo a la investigación. Ministerio de Ciencia e Innovación–Universidad de Salamanca, Spain. |
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Disclosure of potential conflict of interest: C. Teodosio has been supported by one or more grants from Fundação para a Ciência e Tecnologia-Portugal. A. C. García-Montero has been supported by one or more grants from ISCIII and JCyL. C. E. Pedreira has been supported by one or more grants from FAPERJ and CNPq, is employed by the Federal University of Rio de Janeiro, and has received one or more grants from or has one or more grants pending with CNPq, CAPES, FAPERJ. L. Escribano has been supported by one or more grants from the Spanish Ministry of Health. A. Orfao has been supported by one or more grants from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 4
P. 1213 - avril 2013 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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