Alteration in endoglin-related angiogenesis in refractory cytopenia with multilineage dysplasia.
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.
IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain.
Mónica
M
del Rey
Miguel
M
Pericacho
Soraya
S
Velasco
Eva
E
Lumbreras
José Miguel
JM
López-Novoa
Jesús María
JM
Hernández-Rivas
Alicia
A
Rodríguez-Barbero
D000753:Anemia, Refractory / Q000378:metabolism / Q000473:pathology; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A