ABSTRACT
Bone marrow (BM) microenvironment appears to play an important role in the pathogenesis of hematological malignancies. Apart from soluble factors and direct cell-cell contact, the extracellular vesicles (EVs) were identified as a third mediator for cell communication within BM microenvironment. Recently, more and more evidences have demonstrated that EVs are also involved in the dysregulation of the BM microenvironment in patients with hematological malignancies. Therefore this review focuses on the biological characteristics of EVs, the clinical value of EVs as biomarkers, the BM microenvironment reprogramming in hematological malignancies by EVs, and the potential role of EVs in drug resistance and therapy of hematological malignancies.
Subject(s)
Humans , Bone Marrow , Cell Communication , Extracellular Vesicles , Hematologic NeoplasmsABSTRACT
<p><b>OBJECTIVE</b>To investigate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMMSC) in patients with myelodysplastic syndromes (MDS) and to explore the role of BMMSC osteogenic differentiation in the pathogenesis of MDS.</p><p><b>METHODS</b>BMMSC were isolated from bone marrow of patients with MDS and healthy donors, then expanded in vitro. The expression of transcription factor gene RUNX2, Osterix and osteogenic differentiation markers (ALP, BSP, OPN, OCN) were measured by real-time PCR, the alkaline phosphatase(ALP) activity was assessed at 3, 7, 10 days after osteogenic differentiation. Mineralization analysis was performed at day 21 of osteogenic induction.</p><p><b>RESULTS</b>The expression level of RUNX2 and Osterix were significantly decreased in BMMSC from lower-risk MDS patients compared with normal controls (P<0.05). After osteogenic induction, low-risk MDS showed lower alkaline phosphatase activity at day 3 (P<0.05), less intense alizarin red S staining at day 21 (P<0.05), and lower gene expression of osteogenic differentiation markers (P<0.05), however, these expressions in higher-risk MDS were normal.</p><p><b>CONCLUTION</b>BMMSC from low-risk MDS have abnormalities in osteogenic differentiation, it may contribute to the ineffective hamatopoiesis of MDS.</p>
Subject(s)
Humans , Alkaline Phosphatase , Bone Marrow Cells , Cell Differentiation , Gene Expression , Hematopoietic Stem Cells , Myelodysplastic Syndromes , Osteogenesis , Real-Time Polymerase Chain ReactionABSTRACT
Hemopoietic stem cells(HSCs) are regulated by two niches: osteoblastic niche and vascular niche. Osteoblasts are the critical constitutive regulators of the osteoblastic niche. The significance of osteoblasts for hematopoietic disease has not escaped attention. This review attempts to capture the discoveries of the last few years regarding the role of osteoblasts in hematopoietic stem cell niche and relationship between osteoblasts and hematopoietic diseases.
Subject(s)
Animals , Humans , Hematologic Diseases , Hematopoietic Stem Cells , Osteoblasts , Stem Cell NicheABSTRACT
This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P < 0.05). According to WHO criteria, the mRNA expression of Delta-like-1 in RA/RAS, RCMD and RAEB groups were significantly higher than that in normal controls (P < 0.05), the mRNA expression of Jagged-1 in RAEB group was also significantly higher than that in normal controls (P < 0.05). The mRNA expression of Delta-like-1 was significantly correlated with the proportion of blasts in the bone marrow of MDS patients (r = 0.502, P < 0.05). The expression levels of Delta-like-1 and Jagged-1 in MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P < 0.05). The mRNA expression of Delta-like-1 in higher risk group according to International Prognostic Scoring System was significantly higher than that in lower risk group (P < 0.05), there was no significant difference in Jagged-1 expression levels between higher risk group and lower risk group (P > 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.
Subject(s)
Humans , Calcium-Binding Proteins , Genetics , Gene Expression Regulation, Neoplastic , Intercellular Signaling Peptides and Proteins , Genetics , Intracellular Signaling Peptides and Proteins , Genetics , Jagged-1 Protein , Membrane Proteins , Genetics , Mesenchymal Stem Cells , Metabolism , Myelodysplastic Syndromes , Genetics , RNA, Messenger , Serrate-Jagged ProteinsABSTRACT
Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias and high risk of transformation to acute myeloid leukemia.Recently more and more investigations indicate that the abnormality of bone marrow microenvironment is one of important reasons related to MDS. In this article the abnormality of stroma cells, cytokines and signaling pathways in hematopoietic micro-environment of MDS is reviewed.