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Methylation of HAI-2/SPINT2 in Bone Marrow Mesenchymal Stromal Cells of MDS and AML Patients Affects Hematopoietic Stem Cell Survival and Adhesion

Authors :
Fernanda Marconi Roversi
Nathalia Moreno Cury
Fernando V Pericole
Patricia Favaro
Sara Teresinha Olalla Saad
José Andrés Yunes
Marisa Claudia Alvarez De Prax
Karla Priscila Ferro
Matheus Rodrigues Lopes
Source :
Blood. 126:2847-2847
Publication Year :
2015
Publisher :
American Society of Hematology, 2015.

Abstract

In recent years, the role of tumor microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stem/stromal cell (BMMSC) contribution to disease progression remains poorly explored. We had previously performed a microarray analysis of myelodysplastic syndrome (MDS) patient-derived BMMSC (MDS-BMMSC) and found an underexpression of HAI-2/SPINT2, an endogenous inhibitor of the hepatocyte growth factor (HGF) activator. This gene has been described as methylated in various cancer types and has been associated with disease progression. Despite of being related to the pathogenesis of several neoplasms, the role of HAI-2/SPINT2 has not yet been fully elucidated in hematological diseases, such as MDS and acute myeloid leukemia (AML). Thus, the aim of this study was to evaluate HAI-2/SPINT2 expression in derived BMMSC and total bone marrow (BM) of healthy donors (HD), MDS and AML patients as well as in BMMSC treated with 5-Azacitidine (Aza), a DNA methyltransferase (DNMT) inhibitor. To achieve this, we collected BM hematopoietic cells and plastic-adherent BMMSC from aspirates of HD, MDS and AML patients. BMMSC were expanded to passage 4 and defined as CD73+/CD90+/CD105+/CD45-/CD34-/CD31-/HLA-DR-. A total of 29 HD and 121 patients at diagnosis (MDS=72 [low-risk=46, high-risk=26], AML with myelodysplastic related changes (AML-MRC)=17 and de novo AML=32) were included. HAI-2/SPINT2 mRNA was significantly decreased in MDS- (0.34[0.01-2.06];P Disclosures No relevant conflicts of interest to declare.

Details

ISSN :
15280020 and 00064971
Volume :
126
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........bcee8f84d9e683e64d39e85034d4cfcb
Full Text :
https://doi.org/10.1182/blood.v126.23.2847.2847