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

• Published in: Oncotarget Vol. 7; no. 21; pp. 30492 - 30503
• Main Authors: Ramos, Fernando, Robledo, Cristina, Izquierdo-García, Francisco Miguel, Suárez-Vilela, Dimas, Benito, Rocío, Fuertes, Marta, Insunza, Andrés, Barragán, Eva, Del Rey, Mónica, García-Ruiz de Morales, José María, Tormo, Mar, Salido, Eduardo, Zamora, Lurdes, Pedro, Carmen, Sánchez-Del-Real, Javier, Díez-Campelo, María, Del Cañizo, Consuelo, Sanz, Guillermo F, Hernández-Rivas, Jesús María
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 24-05-2016
• Subjects: Adult; Aged; Aged, 80 and over; Bone Marrow - metabolism; Bone Marrow - pathology; Chemokine CXCL10 - blood; Chemokine CXCL9 - blood; DNA Mutational Analysis - methods; Female; Fibrosis; Humans; Male; Middle Aged; Mutation; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; Prognosis; Prospective Studies; Research Paper; Survival Analysis; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; WT1 Proteins - genetics; WT1 Proteins - metabolism; pathogenesis; next-generation sequencing; bone marrow fibrosis; prognosis; myelodysplastic syndromes
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.9026

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.