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Oncotarget. 2016 May 24;7(21):30492-503. doi: 10.18632/oncotarget.9026.

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

Author information

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.

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.

KEYWORDS:

bone marrow fibrosis; myelodysplastic syndromes; next-generation sequencing; pathogenesis; prognosis

PMID:
27127180
PMCID:
PMC5058695
DOI:
10.18632/oncotarget.9026
[Indexed for MEDLINE]
Free PMC Article

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