Excessive generation of reactive oxygen species (ROS) can lead to oxidative-antioxidative imbalance in the organism, resulting in oxidative stress. Hematopoietic stem/progenitor cells (HSPCs) exhibit high sensitivity to changes in ROS levels, and high levels of ROS can impair self-renewal capacity of HSPCs, leading to oxidative damage and even death. Wnt/β-catenin signaling pathway regulates hematopoiesis and plays an important role in determining the fate of stem cells, such as self-renewal, proliferation and differentiation of HSPCs. Studies have shown that Wnt/β-catenin signaling pathway is also closely related to oxidative stress. This article summarizes the relevant literature, and reviews the role of Wnt/β-catenin signaling pathway in oxidative stress, its impact on hematopoietic system, and the current research status of related mechanisms.
Oxidative Stress ; Humans ; Wnt Signaling Pathway ; Hematopoietic Stem Cells ; Reactive Oxygen Species/metabolism* ; Hematopoietic System/metabolism* ; beta Catenin/metabolism* ; Hematopoiesis

The sex-determining region Y-box 7 (Sox7) is a important member of SOX family containing high mobi- lity group (HMG), mapped to human chromosome 8p23.1. Wnt/β-catenin signaling pathway plays an important role in cell survival, differentiation, self-renewal, proliferation and apoptosis, and is closely related with carcinogenesis. SOX7 gene is likely to be a tumor suppressor gene in MDS and other hematological malignancies. As a negative regulator of the WNT/β-catenin signaling pathway, the function loss of this gene can lead to carcinogenesis. The methylation of SOX7 gene leads to the silence of this gene, resulting in tumorigenesis. The decision of hematopoietic stem cells to self-renew or differentiate is a stochastic process, but SOX7 can promote the differentiation into all blood cell types. This review focuses on the role of SOX7 in hematopoietic system development and hematological malignancies.
DNA Methylation ; Gene Silencing ; Hematologic Neoplasms ; genetics ; metabolism ; Hematopoietic System ; physiopathology ; Humans ; SOXF Transcription Factors ; genetics ; metabolism ; Wnt Signaling Pathway

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase, which plays an essential role in cell growth, proliferation and survival. mTOR regulates the transcription of mRNA, synthesis of ribosome and gene expression for metabolism. By forming mTOR complex, it regulates cellular activities by phosphorylating its downstream proteins, such as S6 protein kinase and 4E-BP1. In recent years, the role of mTORC1 in regulating aging is gradually recognized. Studies of physiological function and the regulatory mechanisms of mTOR signaling can not only help to better understand the aging mechanism for cells or organs, but also provide insights as to finding potential new drug targets for aging related diseases. This review focuses on recent advances of mTOR and aging related diseases in hematopoietic and other organ systems.
Aging ; Hematopoietic System ; metabolism ; Humans ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

Signal transducer and activator of transcription 5 (STAT5) is an important transcription factor existing in the cytoplasm of various types of cells. Once activated, STAT5 dimers translocate into nucleus and bind to the corresponding DNA sequence to regulate the transcription of its target genes. There are two isoforms of STAT5: STAT5A and STAT5B with 96% sequence homology and are encoded by two closely related but different genes. Studies have shown that STAT5 can regulate the survival, proliferation, differentiation and death of hematopoietic cells. Furthermore, elevated activation of STAT5 was found in many malignant hematologic diseases and therefore raised the possibility that STAT5 may be used as a new therapeutic target for blood related diseases. This review discusses the regulatory role of STAT5 in hematopoietic cells and its effect on the occurrence and development of blood diseases.
Animals ; Hematologic Diseases ; genetics ; metabolism ; Hematopoietic System ; metabolism ; Humans ; STAT5 Transcription Factor ; genetics ; metabolism

The aim of study was to investigate the regulatory effect of endomorphin-1 (EM-1) on ICAM-1 and VCAM-1 on normal human bone marrow stromal cell surface as well as IL-6 and TNF-α excreted by human normal bone marrow stromal cells. The expression of ICAM-1 and VCAM-1 was determined by flow cytometry, and the concentration of IL-6 and TNF-α was detected by ELISA. The results indicated that the expression of ICAM-1 and VCAM-1 was significantly different from the control group after being cultured with endomorphin-1 for 24 hours (p < 0.05), and different concentrations of endomorphin-1 had no effect on expressions of ICAM-1 and VCAM-1 both; there was no difference in secretion of IL-6 and TNF-α between experimental and control groups (p > 0.05). It is concluded that endomorphin-1 regulates the ICAM-1 and VCAM-1 expression on human normal bone marrow stromal cell surface, but endomorphin-1 does not display any effect on IL-6 and TNF-α secreted by human normal bone marrow stromal cells.
Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Cell Line ; Hematopoietic System ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-6 ; metabolism ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Oligopeptides ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

The aim of this study was to investigate the role of mesenchymal stem cells in the hematopoietic reconstitution of patients who had received haploidentical allogeneic hematopoietic stem cell transplantation (hi-allo-HSCT). 15 patients who underwent treatment with both MSCs and HSCs, were selected as study group, while 20 patients receiving only HSCT were taken as control. Bone marrow samples were obtained from iliac crest aspirates at several times after HSCT for the isolation, purification and expansion of MSCs. The confluent ratio and time were measured and compared with those of the control. The peripheral blood samples were obtained from patients, then absolute neutrophil and platelet counts were assayed. From day 4 before transplantation to day 28 after transplantation, serum was obtained every four days from patients of the two groups, and then 3 cytokines as SDF-1alpha, TPO and IL-11 were detected by ELISA. The results indicated that as compared with the control group, the ratio of primary confluent layer formation of MSCs in study group was obviously higher (27.3%) (p < 0.01), and the confluence time in culture was significantly less (p < 0.05). In the study group, the concentration of SDF-1alpha amounted to peak value (2975.19 +/- 681.56 pg/ml) on the 8th day after HSCT, which was obviously higher than that before HSCT (2403.70 +/- 522.39 pg/ml, p < 0.05), whereas in the control, the concentration of highest point of SDF-1alpha reached to peak valve (2280.60 +/- 701.25 pg/ml) on the 16th day after HSCT, which was less than that before HSCT (2701.46 +/- 483.21 pg/ml, p < 0.05). The concentration of TPO and IL-11 was higher in study group compared with the control from day 16 to 28 after HSCT (p < 0.05). It is concluded that the transfusion of MSCs combined with hi-all-HSCT may improve the injured state of the hematopoietic microenvironment in bone marrow of patients during allo-HSCT.
Adolescent ; Adult ; Bone Marrow ; metabolism ; pathology ; Chemokine CXCL12 ; metabolism ; Child ; Hematopoietic Stem Cell Transplantation ; methods ; Hematopoietic System ; Humans ; Interleukin-11 ; metabolism ; Mesenchymal Stem Cell Transplantation ; methods ; Middle Aged ; Thrombopoietin ; metabolism ; Young Adult

The aim of this study was to detect the expressions of transforming growth factor (TGFβ(1)), tumor necrosis factor alpha (TNFα) and leukemia inhibitory factor (LIF) in newly diagnosed patients with acute myeloid leukemia (AML) and investigate the association between serum levels of various cytokines and clinical outcomes. The levels of TGFβ1, TNFα and LIF in patient's plasma were detected by enzyme-linked immunosorbent assays (ELISA) and were compared with healthy controls; bone marrow cell morphology, immunology, cytogenetics examinations (MIC) were performed meanwhile. The results showed that levels of TGFβ1, TNFα and LIF were elevated in AML patients as compared with the controls (13.08±9.77 ng/ml, 10.67±15.11 pg/ml, 4.23±4.73 pg/ml vs 8.23±3.12 ng/ml, 5.86±3.05 pg/ml, 2.78±1.22 pg/ml) (p all<0.05). The three cytokines and MIC examination analysis indicated that level of LIF was abnormally elevated in M5 patients (7.14±6.62 pg/ml); TNFα was abnormally elevated in M4 and M3 patients especially M4; TGFβ1 level in M6 and M2 patients was higher than others. TGFβ1 plasma concentration in low-risk group the lowest (10.45±4.73 ng/ml), and that in middle risk group was the highest (16.13±13.76 ng/ml) (p<0.05); the levels of other two kinds of factors in the chromosome karyotype groups showed no significant difference. It is concluded that TGFβ1, TNFα and LIF expressions showed increased level in the untreated patients with de novo AML, the TGFβ1 level among which is associated with the prognosis of patients.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Hematopoietic System ; metabolism ; Humans ; Karyotyping ; Leukemia Inhibitory Factor ; blood ; Leukemia, Myeloid, Acute ; blood ; diagnosis ; genetics ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Transforming Growth Factor beta1 ; blood ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

The study was aimed to investigate the effect of deriving hematopoietic cells from human embryonic stem cells (hESCs) by the erythropoietin gene-modified conditioned medium of human mesenchymal cells. The mesenchymal stem cells (MSCs) steadily expressing EPO were established by lentiviral system. The expression of exogenous EPO was detected by RT-PCR and Western blot. After suspension culture, hESCs developed into embryonic bodies (EBs). Then the EB cells were cultured in conditional medium. The hESCs-derived hematopoietic cells were analyzed by immunofluorescence, CFU assay and RT-PCR. The results indicated that the exogenous EPO successfully expressed in the EPO transfected MSCs (EPO/MSCs). The supernatant from EPO/MSCs increased CD34(+) cell population and the expression of globin, and enhanced colony forming unit incidence. These effects were obviously higher than that of control. It is concluded that the EPO gene-modified conditioned medium of human mesenchymal cells can induce the hESCs to differentiate into hematopoietic cells.
Cell Culture Techniques ; Cell Differentiation ; drug effects ; Culture Media, Conditioned ; pharmacology ; Embryonic Stem Cells ; cytology ; drug effects ; Erythropoietin ; genetics ; pharmacology ; Hematopoietic System ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Organisms, Genetically Modified

OBJECTIVETo characterize the structural and the functional feature of a novel gene HSPCSET isolated from human CD34+ hematopoietic stem/progenitor cells (HS/PCs).

METHODSBioinformatic technology was used to identify the structural features of the HSPCSET protein and perform the multiple sequence alignment. Yeast-two-hybrid system was used to identify the proteins interacting with the HSPCSET protein. After sequencing, we selected out the positive clones which had clear functions, and carried out beta-gal experiment and GST pull down assay to confirm the results. The cellular location of the HSPCSET was checked by immunofluorescence assay.

RESULTSThe HSPCSET protein belongs to a SET domain family, which is evolutionarily conserved across species. It implied that HSPCSET may have biologically important function. Using yeast-two-hybrid system, we showed that the protein sequence with SET domain might bind to 13 proteins, which involved in signaling transduction, transcriptional regulation, apoptosis, tumorigenesis, development, etc. And 4 proteins (GADD34, SIVA, DNAJ and PHF1) were confirmed by one-on-one back of the hybrid experiment, beta-gal test and GST pull down assay. When GADD34 and HSPCSET were co-transfected, they co-localized in the nucleus, suggesting a strong interaction.

CONCLUSIONThe novel gene HSPCSET is likely to have biologically important function. This study provides the basis for further studies of its function in hematopoiesis and tumorigenesis.

Amino Acid Sequence ; Animals ; Antigens, Differentiation ; metabolism ; Cell Cycle Proteins ; metabolism ; Computational Biology ; Conserved Sequence ; Hematopoietic Stem Cells ; metabolism ; Humans ; Molecular Sequence Data ; Protein Phosphatase 1 ; Protein Structure, Tertiary ; Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Two-Hybrid System Techniques

OBJECTIVETo explore polarization of T lymphocyte and its relationship with apoptosis of marrow cells in patients with myelodysplastic syndromes (MDS).

METHODSMeasurements of Th1, Th2, Tc1, Tc2 subsets in bone marrows from 34 patients with MDS and 13 normal controls were performed by flow cytometry. INF-gamma and TNF-alpha in marrow serum were determined by ELISA (Enzyme-linked immunosorbent assay). Apoptosis index of marrow cells was detected by TUNEL (TdT-mediated dUTP nick end labeling). Correlations between Th1, Th2, Tc1, Tc2 subsets and INF-gamma, TNF-alpha levels as well as apoptosis index were analyzed, and relationship between TNF-alpha, INF-gamma levels and apoptosis index was also investigated.

RESULTS(1) The percentage of Th1 cells [(10.1 +/- 1.6)%], Tc1 cells [(24.0 +/- 3.6)%] and Tc1/Tc2 ratio (50.0 +/- 11.1) was significantly increased in patients with MDS than in normal controls [(4.0 +/- 0.5)%, (5.8 +/- 0.6)% and 13.4 +/- 2.7, respectively]. Levels of INF-gamma [(58.6 +/- 21.7) microg/L] and TNF-alpha [(15.7 +/- 3.8) microg/L] in marrow serum of MDS patients was markedly elevated compared to normal controls [0 and (0.3 +/- 0.2) microg/L, respectively]. An increased apoptosis index of nucleated cells was observed in MDS patients [(7.8 +/- 1.5)%] as compared to controls [(2.1 +/- 0.3)%, P < 0.05]. The Th1 cell percentage showed a positive correlation with the levels of INF-gamma and TNF-alpha (r = 0.38, P < 0.05 and r = 0.39, P < 0.05, respectively), and with apoptotic index of nucleated marrow cells in MDS patients (r = 0.33, P < 0.05). Furthermore, a positive correlation was observed between INF-gamma, TNF-alpha levels and apoptotic index of marrow cells (r = 0.74, P < 0.01 and r = 0.73, P < 0.01, respectively). (2) Th1, Tc1 cells and Tc1/Tc2 ratio in MDS-RCMD patients was markedly elevated (P < 0.01) but did not in RCMD-RS, RAEB-1 and RAEB-2 patients as compared to normal controls. (3) An elevation in the percentages of Th1, Tcl and Tc1/ Tc2 ratio was detected in patients with IPSS lower-risk but did not in higher-risk group as compared to controls. (4) Increased Th1 and Tc1 percentages and Th1/Th2 and Tc1/Tc2 ratios were observed in RCMD patients with normal karyotype, but did not in those with abnormal karyotype. Conclusions Th1/Th2 and Tc1/Tc2 in bone marrow of MDS patients were unbalanced, polarizing to type I reaction especially in patients with RCMD subtype, IPSS lower-risk and normal karyotype. The increased Th1 cells in bone marrow may account for the increased apoptosis of nucleated marrow cells in MDS, through proapoptotic cytokines such as INF-gamma and TNF-alpha.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; immunology ; Bone Marrow ; immunology ; metabolism ; pathology ; Female ; Hematopoietic System ; immunology ; Humans ; Interferon-gamma ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; T-Lymphocytes ; immunology ; Tumor Necrosis Factor-alpha ; metabolism