Abstract
The functional mechanisms involved in angiogenesis and the potential role of endoglin (ENG), recently described as a new marker for this process, have not been explored in Myelodysplastic Syndromes (MDS). In order to gain insight in MDS angiogenesis a combined analysis in bone marrow (BM) of gene expression levels, angiogenesis-related soluble factors and functional angiogenesis-related studies was carried out. Ninety-seven MDS patients and forty-two normal BM samples were studied. The morphology of the capillary-like structures originated by two endothelial cells lines in the BM environment of patients with refractory cytopenia with multilineage dysplasia (RCMD) was different from those of the remaining MDS. In addition, the BM mononuclear cells from RCMD patients displayed over-expression of VEGF, HIF and FN1 while they showed reduced expression of ENG in contrast to the normal ENG expression of the remaining low-risk MDS and the high expression of ENG in high-risk MDS subtype. Moreover, higher soluble ENG and soluble FLT-1 levels in BM microenvironment were observed in RCMD cases, which distinguished them from other individuals. Therefore, the present study suggests that the patterns of angiogenesis are different between the MDS subtypes. The differences in angiogenesis observed in RCMD patients could be related to ENG abnormalities.
Highlights
Myelodysplastic Syndromes (MDS) are a heterogeneous group of hematopoietic malignancies, characterized by ineffective haematopoiesis, hypercellular bone marrow (BM), dysplasia of at least one lineage and cytopenias in the peripheral blood [1]
The patients with refractory cytopenia with multilineage dysplasia (RCMD) showed an abnormal angiogenesis characterised by an increased level of soluble endoglin
A proliferation assay showed that MDS BM supernatant fluid stimulated bone marrow endothelial cells (BMEC-1) proliferation more than supernatant fluid from controls
Summary
Myelodysplastic Syndromes (MDS) are a heterogeneous group of hematopoietic malignancies, characterized by ineffective haematopoiesis, hypercellular bone marrow (BM), dysplasia of at least one lineage and cytopenias in the peripheral blood [1]. These disorders are classified according to WHO criteria, which take into account types and number of cell dysplasias, percentage of blasts and cytogenetic abnormalities [2,3]. Based on these parameters, MDS can be divided into four prognostic categories: low, intermediate-1, intermediate-2 and high risk [4].
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