DECREASED EXPRESSION OF DECORIN, A WNT-PATHWAY RELATED PROTEIN, IN MESENCHYMAL STEM CELLS OF PATIENTS WITH MYELODYSPLASTIC SYNDROMES
(Abstract release date: 05/18/17)
EHA Library. PAVLAKI K. 05/18/17; 182630; PB1916
KONSTANTIA PAVLAKI
Contributions
Contributions
Abstract
Abstract: PB1916
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are clonal disorders of the haematopoietic stem cells (HSCs) characterized by inefficient bone marrow (BM) haemopoiesis and increased risk for leukaemic evolution. Ineffective BM haemopoiesis in MDS has also been linked with an abnormal microenvironment that may sustain or even induce the aberrations within the HSC compartment. We have previously shown that the stroma progenitor cells, namely the mesenchymal stem cells (MSC), in MDS patients display impaired clonogenic and proliferative potential, reduced haemopoiesis supportive capacity and downregulation of the canonical Wnt-signaling pathway.
Aims
Decorin, a small leucine-rich proteoglycan, and galectin-3, a member of b-galactosidase specific lectin family, are components of the extracellular matrix of the BM microenvironment. Both proteins have been implicated in the canonical Wnt-pathway participating therefore in cell growth and proliferation. The aim of the study is to assess the expression of decorin and galectin-3 in MSCs of MDS patients, evaluating their implication in the abnormal Wnt-signaling previously reported in MDS.
Methods
BM MSCs were isolated from 12 patients with lower risk MDS aged 51 to 75 years (median 67.5 years) and 12 haematologically healthy subjects aged 50 to 73 years (median 63.3 years), after informed consent. The study has been approved by the Ethics Committee of the University Hospital of Heraklion. BM MSCs were characterized according to international system for human cytogenetic nomenclature (ISCN) criteria, expanded and re-seeded for two passages (P). Total RNA was extracted from culture-expanded P2 MSCs and amplified by real-time PCR for the evaluation of decorin and galectin-3. Relative gene expression was calculated by the ΔCt method.
Results
A statistically significant decreased expression of decorin was identified in MSC of MDS patients (mean 1.338, SD 0.84) compared to the healthy individuals (mean 1.830, SD 0.71). (P<0.05). Galectin-3 expression was also decreased in MDS patients (mean 0.6758, SD 0.50) compared to controls (0.9395, SD 0.50), although not at a statistically significant levels.
Conclusion
MSCs from MDS patients display statistically significant decreased expression of decorin and a tendency towards decreased expression of galectin-3 in BM MSCs compared to healthy individuals. These preliminary data indicate that extracellular matrix proteins may have a role in the disturbed Wnt-pathway signaling and abnormal MSC function in MDS patients. The underlying mechanisms are currently under investigation.
Session topic: 9. Myelodysplastic syndromes - Biology
Keyword(s): Mesenchymal stem cell, MDS, Bone marrow stroma
Abstract: PB1916
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are clonal disorders of the haematopoietic stem cells (HSCs) characterized by inefficient bone marrow (BM) haemopoiesis and increased risk for leukaemic evolution. Ineffective BM haemopoiesis in MDS has also been linked with an abnormal microenvironment that may sustain or even induce the aberrations within the HSC compartment. We have previously shown that the stroma progenitor cells, namely the mesenchymal stem cells (MSC), in MDS patients display impaired clonogenic and proliferative potential, reduced haemopoiesis supportive capacity and downregulation of the canonical Wnt-signaling pathway.
Aims
Decorin, a small leucine-rich proteoglycan, and galectin-3, a member of b-galactosidase specific lectin family, are components of the extracellular matrix of the BM microenvironment. Both proteins have been implicated in the canonical Wnt-pathway participating therefore in cell growth and proliferation. The aim of the study is to assess the expression of decorin and galectin-3 in MSCs of MDS patients, evaluating their implication in the abnormal Wnt-signaling previously reported in MDS.
Methods
BM MSCs were isolated from 12 patients with lower risk MDS aged 51 to 75 years (median 67.5 years) and 12 haematologically healthy subjects aged 50 to 73 years (median 63.3 years), after informed consent. The study has been approved by the Ethics Committee of the University Hospital of Heraklion. BM MSCs were characterized according to international system for human cytogenetic nomenclature (ISCN) criteria, expanded and re-seeded for two passages (P). Total RNA was extracted from culture-expanded P2 MSCs and amplified by real-time PCR for the evaluation of decorin and galectin-3. Relative gene expression was calculated by the ΔCt method.
Results
A statistically significant decreased expression of decorin was identified in MSC of MDS patients (mean 1.338, SD 0.84) compared to the healthy individuals (mean 1.830, SD 0.71). (P<0.05). Galectin-3 expression was also decreased in MDS patients (mean 0.6758, SD 0.50) compared to controls (0.9395, SD 0.50), although not at a statistically significant levels.
Conclusion
MSCs from MDS patients display statistically significant decreased expression of decorin and a tendency towards decreased expression of galectin-3 in BM MSCs compared to healthy individuals. These preliminary data indicate that extracellular matrix proteins may have a role in the disturbed Wnt-pathway signaling and abnormal MSC function in MDS patients. The underlying mechanisms are currently under investigation.
Session topic: 9. Myelodysplastic syndromes - Biology
Keyword(s): Mesenchymal stem cell, MDS, Bone marrow stroma
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