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dc.contributor.authorParodi, Stefano
dc.contributor.authorMoretti, Stefano
HAL ID: 739814
ORCID: 0000-0003-3627-3257
dc.contributor.authorGaraventa, Alberto
dc.contributor.authorZanazzo, Giulio
dc.contributor.authorBonassi, Stefano
dc.contributor.authorFardin, Paolo
dc.contributor.authorPistoia, Vito
dc.contributor.authorTonini, Paolo
dc.contributor.authorCorrias, Maria Valeria
dc.contributor.authorMorandi, Fabio
dc.contributor.authorGallo, Fabio
dc.contributor.authorScaruffi, Paola
dc.contributor.authorStigliani, Sara
dc.subjectbone marrow microenvironmenten
dc.subjectIFN signatureen
dc.subjectgene expression profilingen
dc.titleBone marrow of neuroblastoma patients shows downregulation of CXCL12 expression and presence of IFN signatureen
dc.typeArticle accepté pour publication ou publié
dc.contributor.editoruniversityotheraboratory of Oncology, Gaslini Institute, Genoa;Italie
dc.contributor.editoruniversityotherlinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome;Italie
dc.contributor.editoruniversityotherDepartment of Hematology–Oncology, Gaslini Institute, Genoa;Italie
dc.contributor.editoruniversityotherBiostatistics Unit, National Cancer Research Institute, Genoa;Italie
dc.contributor.editoruniversityotherEpidemiology and Biostatistics Section, Gaslini Institute, Genoa;Italie
dc.contributor.editoruniversityotherDepartment of Hematology–Oncology, Burlo Garofalo, Trieste;Italie
dc.contributor.editoruniversityotherTranslational Oncopathology, National Cancer Research Institute, Genoa;Italie
dc.description.abstractenBackground At diagnosis, children with neuroblastoma (NB) present with either localized or metastatic disease. Since the mechanisms responsible for BM invasion are not well known, we investigated the transcriptome of resident BM cells from NB patients as compared to healthy children. Procedure Ninety-two and 88 children with localized and metastatic NB, respectively, and 15 healthy children were included in the study. BM resident cells recovered from BM aspirates by immunomagnetic bead manipulation were subjected to genome-wide microarray analysis. After validation in an independent set of samples, the genes significantly modulated in resident BM cells from NB patients were tested for their diagnostic/prognostic values. Results BM resident cells, irrespective of neoplastic cell invasion, significantly overexpressed genes involved in innate immune responses, and interferon (IFN) and IFN-DRS signatures were enriched. Genes coding for metallothioneins and zinc finger proteins, and involved in histone and nucleosome/chromatin organization were also overexpressed. Resident BM cells from NB patients significantly downregulated genes involved in cell adhesion, and in erythrocyte, myeloid, and platelet differentiation pathways. Among downregulated genes, CXCL12 expression reached near complete silencing in patients with metastatic disease. The downregulation of CXCL12 expression was independent of contact between NB cell and resident BM cell. Conclusions We demonstrated that NB tumor growth at the primary site can alter the BM microenvironment, and the presence of BM-infiltrating NB cells makes the alterations more pronounced. Therefore, the restoration of a BM physiological state by means of IFN-α monoclonal antibody, Sifalimumab, and selective noradrenaline receptor blockers should be further studied to ameliorate patients' clinical management. Pediatr Blood Cancer 2012; 59: 44–51. © 2011 Wiley Periodicals, Inc.en
dc.relation.isversionofjnlnamePediatric Blood & Cancer

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