Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors.

Serotonin enhances megakaryopoiesis and proplatelet formation via p-Erk1/2 and F-actin reorganization.

Our previous studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is a growth factor for hematopoietic stem/progenitor cells. In this study, we proposed a possible mechanism: 5-HT may enhance megakaryopoiesis and proplatelet formation via Erk1/2 pathway and cytoskeleton reorganization. Here, 5-HT(2B)R was first identified in megakaryocytic cells. 5-HT also promoted the megakaryocytes (MKs) proliferation and reduced the cell apoptosis via the activation of 5-HT(2B)R and Akt pathway. The effects were reduced by the 5-HT2B R inhibitor ketanserin. The effect of 5-HT on proplatelet formation in bone marrow MKs were further confirmed: the 5-HT treated group had more proplatelet bearing MKs compared with the control group. To determine whether 5-HT has effects on cytoskeleton reorganization of MKs, and whether these effects could be reduced by ketanserin or Erk1/2 inhibitor PD98059, MKs were stained with the F-actin specific binder rhodamine-phalloidin. The polymerized actin level was lower in the control group than the 5-HT group and was distributed throughout the cytoplasm with occasional aggregations. Our data demonstrated that Erk1/2 was activated in MKs treated with 5-HT. This study suggests that 5-HT has a potent effect on platelet formation and this effect is likely mediated via 5HT(2B)R with subsequent activation of p-Erk1/2 and consequent F-actin reorganization and proplatelet formation. We also demonstrated that melatonin, the metabolite of 5-HT, exerts a protective effect on MK and platelet recovery in the irradiated mouse model. This study suggested that 5-HT plays an important role in platelet formation via 5HT(2B)R, p-Erk1/2, and F-actin reorganization.

Association between MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: a meta-analysis based on 51 case-control studies.

BACKGROUND: Studies and systematic reviews have reached inconsistent conclusions on the role of 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T in acute lymphoblastic leukemia (ALL) risk. MATERIAL AND METHODS: The present meta-analysis comprising of 51 case-control studies, including 7892 cases and 14 280 controls was performed to reevaluate the association between MTHFR C677T polymorphism and ALL risk. RESULTS: Statistical differences were found in the dominant model (TT+CT vs. CC, odd ratio (OR)=0.89, 95% CI, 0.79-1.00, P=0.04) and the CT vs. CC (OR=0.89, 95% CI, 0.80-1.00, P=0.05), but not in the allele contrast model (T vs. C, OR=0.92, 95% CI, 0.84-1.01, P=0.08), additive model (TT vs. CC, OR=0.87, 95% CI, 0.73-1.05, P=0.15), or recessive model (TT vs. CT+CC, OR=0.94, 95% CI, 0.81-1.10, P=0.44) in overall populations. In the subgroup analyses stratified by age (children and adults) and ethnicity (Asian and Caucasian), no significant associations between MTHFR C677T polymorphism and ALL risk were observed. CONCLUSIONS: The current study found no sufficient evidence of a protective role of MTHFR C677T polymorphism in ALL susceptibility.

Circulating CD133(+)VEGFR2 (+) and CD34 (+)VEGFR2 (+) cells and arterial function in patients with beta-thalassaemia major.

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells.

[Expression of Wilms' Tumor 1 Gene in Bone Marrow of Patients with Myelodysplastic Syndrome and Its Clinical Significance].

OBJECTIVE: To investigate the expression level and clinical significance of Wilms' tumor 1 (WT1) in bone marrow of patients with myelodysplastic syndromes (MDS). METHODS: The clinical data of 147 MDS patients who accepted real-time quantitative polymerase chain reaction (RT-PCR) to detect the expression level of WT1 in bone marrow before treated in Nanfang Hospital, Southern Medical University from January 2017 to April 2021 were retrospectively analyzed. According to the expression level of WT1, the patients were divided into WT1+ group and WT1- group, their clinical characteristics and prognosis were analyzed. RESULTS: The positive rate of WT1 in 147 MDS patients was 82.3%. There were significant differences in bone marrow blast count, aberrant karyotypes, WHO 2016 classification, and IPSS-R stratification between WT1+ group and WT1- group (all P<0.05). Furthermore, the higher the malignant degree of MDS subtype and the risk stratification of IPSS-R, the higher expression level of WT1. Compared with WT1- group, there were no differences in overall survival (OS) time and the time of transformation to AML in WT1+ group (both P>0.05). In patients who did not accept transplantation, the median OS time of WT1+ patients was significantly shorter than that of WT1- patients (P=0.049). Besides, regarding WT1+ group, patients who underwent transplantation had longer OS time and lower mortality than those who received hypomethylating agents (P=0.002, P=0.005). CONCLUSION: WT1 expression level directly reflects the disease progression, and it is also associated with prognosis of MDS patients.

The Symptoms and Factors Associated With Posttraumatic Stress Disorder for Burns Nurses: A Cross-Sectional Study From Guangdong Province in China.

The symptoms of posttraumatic stress disorder (PTSD) among medical staff have become a significant issue. Environments related to burns are highly stressful for nurses and can lead to PTSD, thus affecting their mental health. It is vital to consider that the quality of burns care, and the outcomes of such treatments, may be threatened if nurses experience PTSD. We evaluated PTSD symptoms in burns nurses and explored the correlations between demographic characteristics, work-related characteristics, professional identity, turnover intention, and PTSD symptoms. This was a cross-sectional study involving 273 nurses working in the burns unit from Guangdong, China, between July and August 2019. Nurses were recruited from 30 hospitals and completed three validated psychological questionnaires: Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Professional Identity Scale (PIS) for nurses, and Turnover Intention Questionnaire (TIQ). We also collated information relating to sociodemographic and work-related characteristics. The cutoff point for the PCL-C was defined as 38 points; 17.22% (n = 47) of participants scored higher than or equal to 38. The PCL-C score was negatively correlated with professional identity level (P < .01) and positively correlated with turnover intention (P < .01). The workplace, mean monthly income, experience of workplace violence, and professional identity level were important factors and all associated with the severity of PTSD. PTSD symptoms were common in burns nurses. Attention should be paid to the mental well-being of these staff. Screening processes need to be initiated to identify individuals suffering from PTSD and take appropriate early interventional action.

Platelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathway.

BACKGROUND: Platelet-derived growth factor is involved in the regulation of hematopoiesis. Imatinib mesylate, a platelet-derived growth factor receptor inhibitor, induces thrombocytopenia in a significant proportion of patients with chronic myeloid leukemia. Although our previous studies showed that platelet-derived growth factor enhances megakaryocytopoiesis in vitro, the in vivo effect of platelet-derived growth factor in a model of radiation-induced thrombocytopenia has not been reported. DESIGN AND METHODS: In this study, we investigated the effect of platelet-derived growth factor on hematopoietic stem/progenitor cells and platelet production using an irradiated-mouse model. We also explored the potential molecular mechanisms of platelet-derived growth factor on thrombopoiesis in M-07e cells. RESULTS: Platelet-derived growth factor, like thrombopoietin, significantly promoted the recovery of platelets and the formation of bone marrow colony-forming unit-megakaryocyte in irradiated mice. Histology confirmed the protective effect of platelet-derived growth factor, as shown by an increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis. In a megakaryocytic apoptotic model, platelet-derived growth factor had a similar anti-apoptotic effect as thrombopoietin on megakaryocytes. We also demonstrated that platelet-derived growth factor activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression. CONCLUSIONS: Our findings show that platelet-derived growth factor enhances platelet recovery in mice with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via platelet-derived growth factor receptors with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockage of platelet-derived growth factor receptors may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia.

Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway.

BACKGROUND: Dozens of Traditional Chinese Medicine (TCM) formulas have been used for promotion of "blood production" for centuries, and we are interested in developing novel thrombopoietic medicines from these TCMs. Our previous studies have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a formula composed of Radix Angelicae Sinensis and Radix Astragali in animal and cellular models. As a step further to identify and characterize the active chemical components of DBT, we tested the hematopoietic and particularly, thrombopoietic effects of polysaccharide-enriched fractions from the root of Radix Angelicae Sinensis (APS) in this study. METHODS: A myelosuppression mouse model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS, thrombopoietin and vehicle-treated samples were then counted at different time-points. Using the colony-forming unit (CFU) assays, we determined the effects of APS on the proliferation and differentiation of hematopoietic stem/progenitor cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as model, we analyzed the cellular apoptosis progression with and without APS treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays. Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested. RESULTS: In animal models, APS significantly enhanced not only the recovery of platelets, other blood cells and their progenitor cells, but also the formation of Colony Forming Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS. Treatment by Ly294002 alone increased the percentage of cells undergoing apoptosis. However, addition of APS to Ly294002-treated cells significantly reduced the percentage of cells undergoing apoptosis. CONCLUSIONS: APS promotes hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT pathway.

Thrombopoietin levels increased in patients with severe acute respiratory syndrome.

Hematological changes in patients with Severe Acute Respiratory Syndrome (SARS) are common and frequently include thrombocytopenia. Using a ELISA method, we found an increase in thrombopoietin (TPO) levels in the plasma of convalesced SARS patients (290+/-53 pg/ml) and active SARS patients (251+/-23 pg/ml) comparing to that from normal control patients (228+/-17 pg/ml). In addition, the plasma from active SARS patients had an inhibitory effect on CFU-MK formation, which could be neutralized by anti-TGF-beta antibodies. In the experiment to determine whether SARS-CoV can directly infect hematopoietic stem cells and megakaryocytic cells, incubation of the cells with SARS-CoV did not show active infection. Our findings of increased TPO levels in the plasma of SARS patients provide a possible explanation for the genesis of thrombocytosis, which frequently develops from thrombocytopenia in SARS patients.

[Thrombopoietin Prevents CoCl2-inducing Apoptosis of HUVEC through the PI3K/AKT Pathway].

OBJECTIVE: To investigate the effect of thrombopoietin (TPO) on chemical hypoxia-induced apoptosis of human umbilical vein endothelial cells (HUVEC), and to explore its potential mechanism. METHODS: The experiment was divided into 4 groups. The untreated HUVECs were used as normal control group. HUVECs treated with CoCl2 was CoCl2 group, and TPO was added into the culture medium 48 h before CoCl2 treatment as TPO + CoCl2 group. The cells was treated with TPO alone as TPO group. The cell viability and apoptosis of each groups were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in PI3K/AKT pathway was detected by using Western blot. RESULTS: CoCl2 significantly inhibited the growth of HUVECs. The cell viability of HUVECs decreased gradually with enhancement of CoCl2 at a gradient of chemical concentrations (r= -0.997). CoCl2 dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl2 (P<0.001). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl2 (P<0.05). TPO could increased the activation of PI3K/AKT pathway in HUVECs. CONCLUSION: TPO has a protective effect against CoCl2-induced apoptosis of HUVECs through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.

A comparison of two different fluid resuscitation management protocols for pediatric burn patients: A retrospective study.

OBJECTIVE: Pediatric burn patients are more susceptible to burn shock than adults, and an effective fluid management protocol is critical to successful resuscitation. Our research aim was to investigate the safety and efficacy of two protocols for pediatric burn patients for use within the first 24h. METHODS: A total of 113 pediatric burn patients were enrolled from January 2007 to October 2012. Of those patients, 57 received fluid titration regimens of alternating crystalloids and colloids once within 2h in the first 24h after burn (Group A), whereas the remaining patients received regimens of alternating crystalloids and colloids once within 1h in the first 24h after burn (Group B). The safety, fluid volume infused and urine output were recorded and compared. RESULTS: All the patients survived in the first 24h after burn. There were no significant differences between Group A and Group B in lactic acid (LA) level and base excess (BE). The water infused in Group A were greater than that of Group B in the first 24h (P=0.024). No significant differences were found in total volume intake and hourly urine output between the 2 groups in the first 24h. CONCLUSION: The implementation of fluid resuscitation using either protocol A or protocol B is safe and effective for pediatric burn patients in the first 24h. The total fluid infused were similar between two protocols. But using protocol A may be more convenient and labor-saving for nurses.

[PDGF-BB Promotes CFU-GM and CFU-MK Formation and Its Possible Mechnism].

OBJECTIVE: To investigate the effect of platelet-derived growth factor (PDGF-BB) on the formation of granulocyte-monocyte colony forming unit (CFU-GM) and megakaryocyte colony forming unit (CFU-MK) and its anti-apoptotic effect on CHRF cells. METHODS: The CFU-GM and CFU-MK of murine and human bone marrow cells were cultured in vitro by using plasma clot culture system. The anti-apoptotic effect of PDGF-BB on CHRF cells and its mechanism were clarified by flow cytometry. RESULTS: PDGF-BB 0-100 ng/ml stimulated the proliferation of murine and human CFU-GM and CFU-MK in a dose-dependent manner. The maximal stimulation effect was obtained at 50 ng/ml of PDGF-BB (P<0.01). Furthermore, PDGF-BB had an anti-apoptotic effect on CHRF cells as shown by the flow cytometry with AnnexinV/PI double staining, Caspase-3 expression and JC-1 detection (P<0.05). CONCLUSION: PDGF-BB significantly stimulates the proliferation of CFU-GM and CFU-MK in vitro, and has an anti-apoptotic effect on CHRF cells.

[Role of PDGF/PDGFR Pathway in Essential Thrombocythemia and Its Action Mechanism].

OBJECTIVE: To study the role of PDGF/PDGFR in essential thrombocythemia (ET) by investigating the expression of PDGF-BB in bone marrow and the expression of PDGFR-ß in bone marrow cells of patients with ET and explore the new target for treating ET patients through inhibiting the PDGFR of megakaryocytes. METHODS: The expression level of PDGF-BB in bone marrow of ET patients and normal controls were assayed by using ELISA, the expression level of PDGFR-ß (CD140) in bone marrow of ET patients and normal controls were detected by using flow cytometry, the effect of PDGF-BB in JAK2/STAT3 and PI3K/AKT pathway was detected by using flow cytometry or Werstern blot, and the effect of imatinib on the megakaryopoiesis of PDGF was observed. RESULTS: The expression level of PDGF-BB in bone marrow of ET patients was significantly higher than that in normal controls; the expression level of PDGFR-ß in bone marrow of ET patients was significantly higher than that in nornal controls; PDGF-BB could activate JAK2/STAT3 and PI3K/AKT pathway of megakaryocytes, while the imatinib could block the effect of PDGF-BB on megakaryocyte. CONCLUSION: The elevated PDGF-BB and PDGFR-ß may be involved in ET, and the physiopathologic mechanism is that the elevated PDGF-BB activates PDGFR with subsequent activation of the JAK2/STAT3 and PI3K/AKT pathways, stimulating megakaryopoiesis. Imatinib may have a therapeutical effect on ET via blocking of PDGFR.

Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia.

Low concentrations of imatinib (IM) in bone marrow cells have been linked with poor prognosis in patients with chronic myeloid leukemia (CML), which may be caused by the emergence of ATP-binding cassette transporter B1 (ABCB1) mutations. The aim of present study was to investigate how clinical outcomes vary among patients with different single nucleotide polymorphisms (SNPs) of ABCB1. A total of 48 adult patients with CML and higher than median ABCB1 mRNA levels were selected for testing of ABCB1 SNPs. In 28 of the 48 patients, the IM concentration and expression levels of human organic cation transporter 1 (hOCT1) and ABCB1 in bone marrow mononuclear cells (BMMCs) were also tested. Correlations between treatment outcomes and IM concentration or the SNP status of ABCB1 were analyzed. Patients were classified by therapeutic response as major molecular response (MMR) (n=11), complete cytogenetic response (CCyR) (n=19) and non-CCyR (n=18) groups. It was found that the concentration of IM in BMMCs of the CCyR group was significant higher than that of the resistant groups (P=0.013). In addition, the IM concentration was positively correlated with the expression of hOCT1 mRNA (R=0.456, P=0.033), but negatively correlated with the expression of ABCB1 mRNA (R=-0.491, P=0.015). Furthermore, the mRNA expression level of ABCB1 was not associated with therapeutic response, but SNPs of the ABCB1 gene were associated with the response to IM. In conclusion, the concentration of IM in BMMCs may be regulated by the ABCB1 gene, and SNPs of the ABCB1 gene predict the therapeutic response to IM in patients with CML.

[Research and Application of iPS Cells in Blood System].

Induced pluripotent stem cells (iPS cells) were first constructed by Takahshi and et al in 2006. They converted the mouse fibroblasts into ES-like cells via viral transduction with four transcription factors (Oct4, Sox2, Klf4 and c-Myc). Since, the significant progress has been made and many researchers have succeeded in inducing iPS cells from other human somatic cells by some novel approaches, such as combining transcriptional factors and small chemicals. IPS cells have significant prospect in clinical application. IPS cells derived from patient somatic cells can be used as a model in studying the pathogenesis of genetic hematological disease and applied in therapeutic screenings. Recent studies suggested that iPS cells can differentiate into red blood cells and platelets in vitro, which may make up a big blood bank for transfusion in future. In this review, current understanding of both recombinant technology of iPS cells and the research progress in hematology are summarized.

Clinical characteristics of acute lymphoblastic leukemia in male and female patients: A retrospective analysis of 705 patients.

The aim of the present study was to compare the clinical characteristics of acute lymphoblastic leukemia (ALL) that occurred in male and female patients at one institution in Southern China. The medical electronic records of Nanfang Hospital, affiliated to Southern Medical University, were searched for patients with a definite diagnosis of ALL that were diagnosed between January 1, 2001 and December 31, 2012. The clinical data of the patients were collected and analyzed. A total of 705 eligible patients were identified. The gender ratio of male to female patients was 1.84:1. The average ages at the time of diagnosis were 16.43 and 19.54 years for male and female patients, respectively (P=0.007). No significant differences were identified in the seasonal occurrence distribution, blood group distribution or ratio for the presence of the Ph chromosome between males and females. However, a higher incidence of T-cell type ALL was identified in males (P=0.023). The present study reveals that ALL demonstrates a male predominance, but similar clinical characteristics of ALL are present in males and females in Southern China.

[Effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet functions].

The nervous system directly regulates immunity through neurotransmitter receptors expressed on immune cells to participate in host defense and body reparation. Expression of neurotransmitter receptors on blood cells provides important evidence for a direct functional link between the nervous and hematopoietic systems. Our previous studies showed that 5-hydroxytryptamine, as a monoamine neurotransmitter, plays an important role in regulating megakaryocytopoiesis. This review summarizes recent findings of the effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet function, focusing on the receptor expression on hematopoietic stem cells, megakaryocytes/platelets and their functions in order to explore the intrinsic relation of nervous system and hematopoietic system. Based on the existing research results, we find that the monoamine neurotransmitter participates in regulation of megakaryocytopoiesis, and affects on aggregation and functions activation of platelets. Moreover, it has a close link with the specific regulatory factor of megakaryocytopoiesis-TPO. Thus those results also support the "brain-bone marrow-blood-axis" viewpoint of some researchers. At present, the study of the nervous system regulating hematopoiesis is still in its infancy, the exact mechanism remains to be further studied.

[Molecular mechanism of thrombopoietin signal pathways and its new effects].

Thrombopoietin (TPO) is a major cytokine for megakaryocytopoiesis and thrombopoiesis, and also plays an important role in the regulation of early hematopoiesis. TPO activates a number of signal pathways to exert its biological function by binding to its receptor (c-mpl). Once these signal pathways (including Jak/STAT, PI3K/Akt, Ras/MAPK) are activated, the expression of the downstream signal molecules can be changed, which then induces biological effects. Recent researches have suggested the novel functions of TPO in many systems. The receptor of TPO (c-mpl) has been shown not only present in hematological cells, but also in many other cells and organs, such as neurons, heart muscle cells, vessel endothelial cells and so on. TPO exerts a protective effect on these cells through the interaction with c-mpl. This review discusses the molecular mechanism of TPO signal and the effect of TPO on multi-nonhematopoietic cells.

[Anti-apoptotic effect of Astragalus Polysaccharide on myeloid cells].

This study was aimed to assess the effect of Astragalus Polysaccharide (ASPS) on in-vitro hematopoiesis. CFU-GM assays were used to determine the effect of ASPS and thrombopoietin (TPO) on granulocytic-monocyte progenitor cells. The CFU assays were also used to investigate the effect of ASPS on the proliferation of HL-60 cells.HL-60 cells were cultured with serum-free RPMI 1640 medium and treated with or without of different concentrations of ASPS. After 72 h incubation, the number of cells were counted.In addition, the caspase-3 and JC-1 expression was determined by flow cytometry with Annexin V/PI double staining. The results showed that ASPS (100, 200 µg/ml) and TPO (100 ng/ml) significantly promoted CFU-GM formation in vitro. Various concentrations of ASPS and TPO also promoted the colony formation of HL-60 cells, the largest effect of ASPS was observed at a concentration of 100 µg/ml. There were no synergistic effects between TPO and ASPS on cellular proliferation. The results also showed that ASPS significantly protected HL-60 cells from apoptosis in condition of serum-free medium culture, suppressed caspase 3 activation, and reduced the cell apoptosis. It is concluded that ASPS can significantly promote the formation of bone marrow CFU-GM and the proliferation of HL-60 cells, the optimal concentration of ASPS is at 100 µg/ml. In the absence of serum inducing apoptosis, ASPS also significantly reduced the apoptosis of HL-60 cells via suppressing the activation of caspase-3.

Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways.

In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP, Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.