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

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.

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population‐based setting: a report from the Swedish MDS register

“…Elevated LDH is a disease feature previously reported to be associated with poor survival in MDS (Greenberg et al , ). A negative prognostic value of bone marrow fibrosis has been observed in some (van Spronsen et al , ; Ramos et al , ) but not in all studies (Greenberg et al , ). In unadjusted analyses, patients with fibrosis ≥ grade 2 had a shorter median OS in our study but not in adjusted analyses.…”

Mutational analysis of disease relapse in patients allografted for acute myeloid leukemia

“…Both TET2 mutations have previously been reported in myelodysplastic syndrome. 34 Finally, in 2 patients (65 and 92), complex and distinct changes in clonal structures occurred from diagnosis to pre-allo-SCT (presumably reflecting selection by IC or possibly de novo mutation), and from pre-allo-SCT to relapse ( Figure 4C; summarized in Figure 4D and supplemental Tables 4 and 5). …”

Bone marrow fibrosis at diagnosis is associated with TP53 overexpression and adverse prognosis in low‐risk myelodysplastic syndrome

“…Similarly, Ramos et al (2016) showed an association between bone marrow fibrosis and TP53 protein accumulation. It is possible that there is a biological interaction between mutations in the TP53 gene and bone marrow fibrosis; however, these mechanisms have yet to be elucidated.…”

“…Bone marrow fibrosis is a histological finding in approximately 10-20% of patients with de novo MDS; however, MDS with fibrosis is not yet recognized as a distinct entity and its prognostic role is still under debate (Ramos et al, 2016).…”