Endothelial progenitor cell dysfunction in myelodysplastic syndromes: possible contribution of a defective vascular niche to myelodysplasia

Luciana Teofili, Maurizio Martini, Luigi Maria Larocca, Eugenia Rosa Nuzzolo, Sara Capodimonti, Maria Grazia Iachininoto, Alessandra Cocomazzi, Emiliano Fabiani, Maria Teresa Voso

Risultato della ricerca: Contributo in rivistaArticolo in rivista

17 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)401-409
Numero di pagine9
RivistaNeoplasia
Volume17
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Endothelial Cells
  • Myelodysplastic Syndromes

Fingerprint Entra nei temi di ricerca di 'Endothelial progenitor cell dysfunction in myelodysplastic syndromes: possible contribution of a defective vascular niche to myelodysplasia'. Insieme formano una fingerprint unica.

Cita questo