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Objective To investigate the expression of sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9)/E ligands in hypoxic condition and its effect on platelet activation. Methods The distribution, molecular size and glycoprotein class of Siglec-9 ligands on platelet were determined. The platelets were divided into control group and neuraminidase group [treated with α2-3, 6, 8 neuraminidase (NEU1)]. Twenty-four C57BL/6 male mice (6~8 weeks old) or cultured platelets were treated with or without hypoxia, and then the mice were divided into control 3-day group, hypoxia 3-day group, control 7-day group and hypoxia 7-day group, with 6 mice in each group. The platelets were separated and extracted from the whole blood of healthy volunteers and were placed in a hypoxia chamber, and then divided into control group, hypoxia 48-hour group, GT1b group and oseltamivir group (n=3). The expression of Siglec-E/9 ligands, NEU1, and CD62p which was activated by adenosine diphosphate (ADP), collagen and thrombin on the platelet were detected by flow cytometry. The inhibitory effect of Siglec-E/9 ligands was verified using conditional knockout mice Lyz2-cre: Siglec-Eflox/flox (male, 6~8 weeks old, n=6). Results Siglec-9 ligands are sialoglycoproteins with molecular weights of about 130×103 and are distributed broadly on the membrane of platelet. In vivo, the expression of Siglec-E ligands was decreased by 18.03% in response to hypoxia treatment (P < 0.05), and the stimulation of ADP, collagen and thrombin resulted in obviously elevated CD62p level in the platelets from the hypoxia 7-day group than those from the control 7-day group (P < 0.01). Similar Results were observed in the platelets of the hypoxia 48-hour group (P < 0.01). Compared with the platelets from wild-type mice, the platelets from the knockdown mice had significantly higher expression of CD62p after the stimulation of ADP, collagen and thrombin (P < 0.01). GT1b treatment could reverse the abnormal platelet activation induced by hypoxia (P < 0.05), and treatment of oseltamivir, NEU1 inhibitor could block the decreased expression of Siglec-9 ligand caused by hypoxia (P < 0.05). Conclusion Hypoxia can decrease the expression of Siglec-9/E ligands, reduce Siglec-9/E-mediated platelet activation, and thus lead to abnormal activation of platelets, which is associated with the increased expression of NEU1.

Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis. [ABSTRACT FROM AUTHOR]

Fetal liver tyrosine kinase 3 ( FLT3)-internal tandem duplications ( ITDs) has been used as a powerful adverse prognostic indicator for acute myeloid leukemia ( AML) in any age group. Evidence is mixed regarding the effects of allogeneic transplantation (allo- HSCT) in first complete remission ( CR) for patients with FLT3/ ITD AML. To fill this gap, this study provides a systematic review and meta-analysis of patients with FLT3/ ITD AML receiving HSCT. A search of PubMed, Embase, and OVID yielded 1706 abstracts, two researchers screening the trials based on inclusion and exclusion criteria, and assessed the methodology quality independently. Meta-analysis showed that compared with chemotherapy, both allo- HSCT and autologous hematopoietic cell transplantation (auto- HSCT) can reduce the relapse rate (p < 0.01) and improve both the OS (p < 0.01) and DFS (p < 0.01). But when compared allo- HSCT with auto- HSCT, the OS (p = 0.27) and DFS (p = 0.19) have no statistical significance, and only the relapse indicator has statistical significance, p < 0.01. Based on the results, we can conclude that allo- HSCT is an efficient therapy approach for patients with FLT3/ ITD AML. Chemotherapy cannot change the poor prognosis. Auto- HSCT can improve OS and DFS, but it cannot reduce the relapse rate. [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic transplantation with human umbilical cord blood (hUCB) in adult recipients is mainly limited by a low CD34+ cell dose. To break the limit, hUCB as a novel source of hUCB-derived stromal cells was incorporated in an attempt to expand CD34+ cells from hUCB in vitro. Cord blood CD34+ cells were separated by MACS system. HUCB-derived stromal cells were cultured by the Dexter system and characterized by morphologic, immunophenotypical, and functional analysis. We studied the effects of hUCB-derived stromal cells, cytokines, and hUCB-derived stromal cells combined with cytokines on expansion of hUCB CD34+ cells. The CD34+ cells were assessed for the degree of expansion and the number of colony-forming units in semisolid culture. Our research found that hUCB-derived stromal cells were mainly composed of three kinds of cell components, with CD106, CD29, CD44, CD45, CD50, CD68, CD31, Fn, Lm, and collagen IV positive, but CD34 negative immunophenotype. Functionally, it was discovered by cell cycle and growth curve analyses that the capability of colony and parietal layer formation of hUCB-derived stromal cells was poorer than that of BM stromal cells, and the doubling time of hUCB-derived stromal cells was longer than that of BM stromal cells. It was indicated by ELISA and RT-PCR that hUCB-derived stromal cells express higher level of TPO and less GM-CSF and SCF than BM stromal cell. Adherent layer of hUCB-derived stromal cells alone or combining with cytokines, increased CD34+ cell expansion. In vitro formation of CFUs by expanded CD34+ cells was significantly higher than that of unexpanded CD34+ cells (P < 0.05). When cocultured with hUCB-derived stromal cells in the presence of cytokines, cell growth was significantly enhanced: CD34+ cells by 8.02 ± 0.96-fold, CFU-GM by 217.60 ± 6.72-fold, CFU-E by 1940.80 ± 52.78-fold, and CFU-Mg by 142.60 ± 4.39-fold. HUCB-derived stromal cells have significant superiority on the expansion of CFU-Mg (P < 0.05). The results indicate that human umbilical cord blood-derived stromal cells may be a suitable feeder layer for expansion of hematopoietic progenitors from hUCB in vitro. [Copyright &y& Elsevier]

Background: Acute myeloid leukemia (AML) is a type of hematological tumor caused by malignant clone hematopoietic stem cells. The relationship between lncRNAs and tumor occurrence and progression has been gaining attention. Research has shown that Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) is abnormally expressed in various diseases, whereas its role in AML is still poorly understood., Methods: The expression of SENCR, microRNA-4731-5p (miR-4731-5p) and Interferon regulatory factor 2 (IRF2) were measured using qRT-PCR. The proliferation, cycle and apoptosis of AML cells with or without knockdown of SENCR were detected by CCK-8 assay, EdU assay, flow cytometry, western blotting and TUNEL assay, respectively. Consistently, SENCR knockdown was impaired the AML progression in immunodeficient mice. In addition, the binding of miR-4731-5p to SENCR or IRF2 was confirmed by luciferase reporter genes assay. Finally, rescue experiments were conducted to confirm the role of SENCR/miR-4731-5p/IRF2 axis in AML., Results: SENCR is highly expressed in AML patients and cell lines. The patients with high SENCR expression had poorer prognosis compared with those with low SENCR expression. Interestingly, knockdown of SENCR inhibits the growth of AML cells. Further results demonstrated that the reduction of SENCR slows the progression of AML in vivo. SENCR could function as a competing endogenous RNA (ceRNA) to negatively regulate miR-4731-5p in AML cells. Furthermore, IRF2 was validated as a direct target gene of miR-4731-5p in AML cells., Conclusions: Our findings underscore the important role of SENCR in regulating the malignant phenotype of AML cells by targeting the miR-4731-5p/IRF2 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Despite the availability of various anticancer agents, Multiple Myeloma (MM) remains incurable in most cases, along with high relapse rate in the patients treated with these agents. The year 2015 saw major advancements in our battle against multiple myeloma. In 2015, the U.S. Food and Drug Administration (FDA) approved three new therapies for multiple myeloma, namely Ixazomib (an oral proteasome inhibitor), Daratumumab and Elotuzumab (monoclonal antibodies against CD38 and SLAMF7 respectively). The purpose of this review is to provide a detailed analysis of these aforementioned breakthrough therapies and two other newer agents, Filanesib (kinesis spindle inhibitor) and selinexor (SINE inhibitor), presented at the 2015 annual meeting of American Society of Hematology (ASH). We also describe the role of agents targeting PD-1 axis and chimeric antigen receptor T (CAR-T) cells in the treatment of MM.