Abstract:
OBJECTIVE:Thrombopoietin stimulates megakaryopoiesis and platelet production by binding to its receptor, Mpl, on hematopoietic progenitor cells. Previously, a murine VB22B minibody for Mpl was shown to stimulate megakaryocyte colony formation in vitro and increase the platelet count in cynomolgus monkeys. In this study, we directly compared the effects of a humanized VB22B minibody (huVB22B) with those of thrombopoietin and eltrombopag under the hypothesis that Mpl agonists might have different biological effects on megakaryopoiesis, platelet production, intracellular signal transduction, and platelet function. MATERIALS AND METHODS:Human bone marrow-derived CD34(+) cells were used for colony formation assays and proplatelet formation assays in vitro. The DNA ploidy in megakaryocytes was analyzed by flow cytometry. Phosphorylation of signal transducers and activators of transcription and mitogen-activated protein kinase was detected by Western blotting using specific antibodies. The effects of the Mpl agonists on platelet aggregation were analyzed by aggregometry using human platelets. RESULTS:HuVB22B was as potent as thrombopoietin and eltrombopag in its ability to form mature megakaryocytes using human CD34(+) cells in vitro. It did not affect granulocyte-macrophage or erythroid colony formation. HuVB22B increased the number of proplatelet-forming megakaryocytes more efficiently than thrombopoietin or eltrombopag. Despite stronger phosphorylation of signal transducers and activators of transcription and mitogen-activated protein kinase compared with thrombopoietin in human platelets, huVB22B did not enhance adenosine diphosphate- or collagen-induced platelet aggregation. Eltrombopag did not enhance agonist-induced platelet aggregation. CONCLUSIONS:We found that huVB22B, eltrombopag, and thrombopoietin have different effects on megakaryopoiesis, platelet function, and intracellular signaling. The precise mechanisms for these different biological effects regarding stimulation through the same receptor, Mpl, remain to be elucidated.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Matsuki E,Miyakawa Y,Yamane A,Okamoto Sdoi
10.1016/j.exphem.2011.05.001subject
Has Abstractpub_date
2011-08-01 00:00:00pages
829-36issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(11)00188-3journal_volume
39pub_type
杂志文章abstract:OBJECTIVE:Approximately 60% of all anaplastic large-cell lymphomas (ALCL) contain a specific t(2;5)(p23;q35) chromosomal translocation leading to overexpression of NPM-ALK. As the chimeric tyrosine kinase is involved in tumorigenesis and pathogenesis of ALCL, we were interested to inhibit NPM-ALK expression using an ex...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)01084-6
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a prog...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.05.007
更新日期:2005-08-01 00:00:00
abstract::Current next-generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumors. Recent studies in myeloproliferative neoplasms have further demonstrated that, not only the mutational profile, but also the order in which these mutations are acquired is relevant for our underst...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.09.011
更新日期:2018-01-01 00:00:00
abstract::We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00029-0
更新日期:1999-03-01 00:00:00
abstract::Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescenc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Improvement in diagnostic cytogenetic techniques has led to the recognition of an increasing number of leukemia-associated chromosomal translocations and inversions. These genetic lesions frequently are associated with the disruption of putative transcription factors and the production of hybrid transcripts that are i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00082-x
更新日期:1999-09-01 00:00:00
abstract::Cells for study were obtained from mouse bone marrow by three methods: 1) Mechanical dissociation; 2) Trypsin release; and 3) Passage through a syringe and needle. The ratio of the fibroblast colony-forming cells in these suspensions was, respectively, 1:13:1. Of the colonies formed by cells obtained by trypsin releas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematop...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.01.002
更新日期:2014-05-01 00:00:00
abstract::CD34 is a cell-surface glycoprotein expressed in a developmental, stage-specific manner by bone marrow stem and progenitor cells. In this study we explored a possible role for c-Myb in CD34 regulation during developmental hematopoiesis. The results indicate that c-Myb can induce CD34 expression in hematopoietic and no...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and norma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract:BACKGROUND:In patients treated with rituximab and alemtuzumab for lymphomas or CLL, antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action. Therefore, assessment of ADCC is mandatory to understand the complex mechanisms leading to the anti-lymphoma effects of monoclonal antibodies (mAb). Due to ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.02.015
更新日期:2006-06-01 00:00:00
abstract::Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::The relative contributions of various organs to platelet production is controversial. In this study, serial histologic sections of bone marrow, spleen, liver, and lung from normal C57BL/6J mice and mice that had received three different agents which perturb normal murine thrombopoiesis (platelet antiserum, 5-fluoroura...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::In chronic eosinophilic leukemia, the transforming oncoprotein FIP1L1-PDGFRA is a major target of therapy. In most patients, the tyrosine kinase inhibitor (TKI) imatinib induces complete remission. For patients who are intolerant or resistant, novel TKIs have been proposed. We examined the in vitro effects of 14 kinas...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2013.12.007
更新日期:2014-04-01 00:00:00
abstract::Hematopoietic cells have the potential for providing benefit in a variety of clinical settings. These include cells for support of patients undergoing high-dose chemotherapy, as a target for replacement gene therapy, and as a source of cells for immunotherapy. The limitation to many of these applications has been the ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/s0301-472x(00)00610-x
更新日期:2001-01-01 00:00:00
abstract::Improving our understanding of the intricacies of hematopoietic specification of induced or embryonic human pluripotent stem cells is beneficial for many areas of research and translational medicine. Currently, it is not clear whether, during human pluripotent stem cells hematopoietic differentiation in vitro, the mat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.05.007
更新日期:2018-09-01 00:00:00
abstract::Hematopoietic progenitor cells (low density, lineage negative [Lin-], depleted of CD4+, CD8+, B220+, Gr-1+, Mac-1+, CD71+, and Thy1.2+ cells) can engraft lethally irradiated mice when transplanted within, but not across the major histocompatibility (MHC) antigen barrier. We hypothesized that our progenitor cell prepar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::The long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic prol...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) ass...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.05.002
更新日期:2013-10-01 00:00:00
abstract::The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVE:The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex netw...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.02.009
更新日期:2008-07-01 00:00:00
abstract::In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.12.003
更新日期:2016-04-01 00:00:00
abstract::Marked loss of colony stimulating activity was noted when the highly purified human urinary colony stimulating factor (CSFHU-5) dissolved in 0.1 M Tris-HCl buffer (pH 7) was passed through ethylene oxide sterilized Millipore filters. The addition of 0.5 mg/ml polyethylene glycol (PEG) or 10 mg/ml bovine serum albumin ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of ty...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::The aberrant overexpression of Wilms tumor-1 (WT1) in acute myeloid leukemia (AML) plays an important role in blast cell survival by enhancing proliferation and inhibiting apoptosis. However, the mechanism underlying the overexpression of WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600 targ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.02.001
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:Adenoviral vectors (Ad) were widely used in gene therapy and study of gene function, but the commonly used serotype 5 adenovirus-based vectors (Ad5) could poorly transduce hematopoietic cells because of low expression of viral receptors on these cells. To overcome this limitation, we developed a retargeting a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.005
更新日期:2006-09-01 00:00:00
abstract::T(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in infant and pediatric populations. Epidemiological and functional studies have highlighted the influence of an overstimulation of the immune system on leukemia development. This study aimed at assessing if the cell-of-origin of t(4;11) MLL-AF4...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.07.004
更新日期:2019-08-01 00:00:00