Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis.

Ramos, Fernando; Robledo, Cristina; Izquierdo-García, Francisco Miguel; Suárez-Vilela, Dimas; Benito, Rocío; Fuertes, Marta; Insunza, Andrés; Barragán, Eva; Rey, Mónica del; García-Ruiz de Morales, José María; Tormo, Mar; Salido, Eduardo; Zamora, Lurdes; Pedro Olive, Carme; Sánchez-del-Real, Javier; Díez-Campelo, María; Cañizo, Consuelo del; Sanz, Guillermo F.; Hernández-Rivas, Jesús María; Spanish Group for Myelodysplastic Syndromes (GESMD)

Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis.

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dc.contributor.author Ramos, Fernandoca
dc.contributor.author Robledo, Cristinaca
dc.contributor.author Izquierdo-García, Francisco Miguelca
dc.contributor.author Suárez-Vilela, Dimasca
dc.contributor.author Benito, Rocíoca
dc.contributor.author Fuertes, Martaca
dc.contributor.author Insunza, Andrésca
dc.contributor.author Barragán, Evaca
dc.contributor.author Rey, Mónica delca
dc.contributor.author García-Ruiz de Morales, José Maríaca
dc.contributor.author Tormo, Marca
dc.contributor.author Salido, Eduardoca
dc.contributor.author Zamora, Lurdesca
dc.contributor.author Pedro Olive, Carmeca
dc.contributor.author Sánchez-del-Real, Javierca
dc.contributor.author Díez-Campelo, Maríaca
dc.contributor.author Cañizo, Consuelo delca
dc.contributor.author Sanz, Guillermo F.ca
dc.contributor.author Hernández-Rivas, Jesús Maríaca
dc.contributor.author Spanish Group for Myelodysplastic Syndromes (GESMD)ca
dc.date.accessioned 2016-10-24T11:13:45Z
dc.date.available 2016-10-24T11:13:45Z
dc.date.issued 2016
dc.description.abstract The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB,and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis.ca
dc.description.sponsorship This work was partially supported by research funding from Celgene S.L., Madrid, Spain, by the Fundación Española de Hematología y Hemoterapia (FEHH) (MDR) and by grants (RD12/0036/0069 and RD12/0036/0044) from the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF) “Una manera de hacer Europa”; Junta de Castilla y León (GRS 994/A/14, BIO/SA47/13 and GRS 1033/A/14). The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement no. 306242-NGS-PTL.
dc.format.mimetype application/pdfca
dc.identifier.citation Ramos F, Robledo C, Izquierdo-García FM, Suárez-Vilela D, Benito R, Fuertes M. et al. Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis. Oncotarget. 2016 May 24;7(21):30492-503. doi: 10.18632/oncotarget.9026ca
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.9026
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/27425
dc.language.iso engca
dc.publisher Impact Journalsca
dc.relation.ispartof Oncotarget. 2016 May 24;7(21):30492-503
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/306242
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.keyword Myelodysplastic syndromes
dc.subject.keyword Bone marrow fibrosis
dc.subject.keyword Next-generation sequencing
dc.subject.keyword Pathogenesis
dc.subject.keyword Prognosis
dc.title Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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