title: Endothelial progenitor cell dysfunction in myelodysplastic syndromes: possible contribution of a defective vascular niche to myelodysplasia.
abstract: We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs), and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS). Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt) pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Teofili
authors.affiliation: Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Eugenia Rosa
authors.initials: ER
authors.lastname: Nuzzolo
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Iachininoto
authors.affiliation: Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cocomazzi
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fabiani
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: llarocca@rm.unicatt.it.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D000368:Aged; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D055153:Stem Cell Niche / Q000502:physiology*