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

2016; Impact Journals LLC; Volume: 7; Issue: 21 Linguagem: Inglês

10.18632/oncotarget.9026

1949-2553

Fernando Ramos, Cristina Robledo, Francisco Miguel Izquierdo-García, Dimas Suárez‐Vilela, Rocí­o Benito, M. Fuertes, A. Insunza, Eva Barragán, Mónica del Rey, José María García-Ruiz de Morales, Mar Tormo, Eduardo Salido, Lurdes Zamora, Carmen Pedro, Javier Sánchez‐del‐Real, María Díez‐Campelo, Consuelo del Cañizo, Guillermo Sanz, Jesús María Hernández‐Rivas,

Bone and Joint Diseases

// Fernando Ramos 1,2 , Cristina Robledo 3 , Francisco Miguel Izquierdo-García 4 , Dimas Suárez-Vilela 5 , Rocío Benito 3 , Marta Fuertes 1 , Andrés Insunza 6 , Eva Barragán 7 , Mónica del Rey 3 , José María García-Ruiz de Morales 8 , Mar Tormo 9 , Eduardo Salido 10 , Lurdes Zamora 11 , Carmen Pedro 12 , Javier Sánchez-del-Real 1 , María Díez-Campelo 13 , Consuelo del Cañizo 13 , Guillermo F. Sanz 14 and Jesús María Hernández-Rivas 3,13 ; Spanish Group for Myelodysplastic Syndromes (GESMD) 1 Department of Hematology, Hospital Universitario de León, León, Spain 2 Instituto de Biomedicina (IBIOMED), Universidad de León, León, Spain 3 Unidad de Diagnóstico Molecular y Celular del Cáncer, IBSAL, IBMCC-Centro de Investigación del Cáncer (USAL-CSIC), Salamanca, Spain 4 Department of Pathology, Hospital Universitario de León, León, Spain 5 Department of Pathology, Hospital Valle del Nalón, Langreo-Asturias, Spain 6 Department of Hematology, Hospital Universitario U. Marqués de Valdecilla, Santander, Spain 7 Department of Molecular Pathology, Hospital Universitari i Politècnic La Fe, Valencia, Spain 8 Department of Immunology, Hospital Universitario de León, León, Spain 9 Department of Hematology-Oncology, Hospital Clínico Universitario, Valencia, Spain 10 Department of Hematology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain 11 Unit of Molecular Genetics, ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras, Badalona, Spain 12 Department of Hematology, Hospital del Mar, Barcelona, Spain 13 Department of Hematology, Hospital Universitario de Salamanca, Spain 14 Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain Correspondence to: Fernando Ramos, email: // Keywords : myelodysplastic syndromes, bone marrow fibrosis, next-generation sequencing, pathogenesis , prognosis Received : February 09, 2016 Accepted : April 17, 2016 Published : April 26, 2016 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.