Abstract
The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.
Highlights
Myelodysplastic syndromes (MDS) are a group of diseases derived from malignant amplification of hematopoietic stem cells (HSCs), with typical features of abnormal myeloid cell differentiation and maturation, ineffective hematopoiesis, and a high risk of progression to acute myeloid leukemia [1]
Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-b in the myelodysplastic syndromes (MDS) group were significantly downregulated (P,0.05), while interferon-c (IFN-c), tumor necrosis factor-a (TNFa), and programmed death ligand (B7-H1) were significantly upregulated (P,0.05)
We found that the expression levels of cytokines including leukemia inhibitory factor (LIF), SCF, SDF-1, bone morphogenetic protein 4 (BMP-4), FLT-3, and transforming growth factor-b (TGF-b) were significantly downregulated in the bone marrow microenvironment of MDS patients
Summary
Myelodysplastic syndromes (MDS) are a group of diseases derived from malignant amplification of hematopoietic stem cells (HSCs), with typical features of abnormal myeloid cell differentiation and maturation, ineffective hematopoiesis, and a high risk of progression to acute myeloid leukemia [1]. The incidence and prevalence of MDS are higher in males than in females and increase sharply with age [2,3]. With the aging population and improving awareness of the disease, the documented disease burden is predicted to escalate in the near future. The age of onset is younger in Asia than in Western countries, [4,5]. There is an urgent need to develop new therapeutic options and clinical management of MDS, which must be based on diagnostic efficiency and knowledge of the pathology of MDS. MDS must be distinguished from anemia, thrombocytopenia, and leukopenia [9,10]. It is important to find specific pathological hallmarks for improving diagnostic efficiency
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