Abstract:
OBJECTIVE:We have recently reported that 20% O2 significantly enhances total megakaryocyte (Mk) number, polyploidy, and proplatelet formation compared to 5% O2 in culture. In order to further elucidate the regulatory role of pO2 on megakaryocytopoiesis, we conducted a kinetic study of the expression of surface markers CD41a and CD42a; receptors for thrombopoietin (TPO), interleukin-3 (IL-3), and Flt3-ligand; the glutamate receptor of the N-methyl-D-aspartate subtype 1 (NMDAR1); and transcription factors GATA-1, NF-E2, and E2F-1. MATERIALS AND METHODS:Mks were generated from mobilized peripheral blood (PB) CD34+ cells from normal donors in serum-free medium with TPO, IL-3, and Flt3-ligand at 20% and 5% O2. Quantitative assessment of Mk surface receptors and nuclear transcription factors was performed using multiparameter flow cytometry. mRNA levels of the nuclear transcription factors GATA-1 and NF-E2 were evaluated using RT-PCR. RESULTS:The proportions of cells expressing the early Mk marker CD41a and the late Mk marker CD42a at day 15 were 4 and 5 times higher, respectively, at 20% O2. CD41a and CD42a protein levels per cell were also higher at 20% O2. After day 5, c-Mpl (TPO receptor) generally followed similar kinetics as CD41a. The proportion of IL-3 receptor (IL-3R)++ Mks at day 5 was 1.5 times higher at 5% O2. The NMDAR1 protein previously known to be expressed by neuronal cells has recently been identified in Mks. NMDAR1 and the transcription factors were studied on days 6, 9, and 11. NMDAR1 was expressed at a 1.5- to 1.8-fold higher level at 5% O2. Twenty percent O2 supported higher expression of the Mk-early and -late-maturation-specific transcription factors GATA-1 (1.2- to 2.2-fold higher) and NF-E2 (1.1- to 2.8-fold higher). This was consistent with RT-PCR data indicating the presence of higher levels of GATA-1 and NF-E2 mRNA at 20% O2. E2F-1, a ubiquitously expressed cell cycle transcription factor, was expressed at a 1.5-fold higher level at 20% O2 on day 6, but this difference did not persist by day 9. CONCLUSION:These findings demonstrate that cytokine receptors c-Mpl and IL-3R, and Mk differentiation-specific surface receptors CD41a, CD42a, and NMDAR1, are significantly modulated by pO2, and suggest that one of the mechanisms of enhanced maturation at 20% O2 may involve regulation of transcription factors GATA-1 and NF-E2.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Mostafa SS,Papoutsakis ET,Miller WMdoi
10.1016/s0301-472x(01)00658-0keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
873-83issue
7eissn
0301-472Xissn
1873-2399pii
S0301-472X(01)00658-0journal_volume
29pub_type
杂志文章abstract::Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS:NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00669-x
更新日期:2001-03-01 00:00:00
abstract::Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::A thymic stromal cell line with a medullary phenotype (Z210R.1) supported the differentiation of surface IgM+ B cells when cocultured with fetal liver cells in vitro. Conditioned medium (CM) from this cell line supported the long-term growth of a B cell line (NAG8/7) isolated from cocultures and enhanced the prolifera...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract:OBJECTIVE:We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.06.009
更新日期:2009-10-01 00:00:00
abstract::Immunoenzymatic (IE) staining for antigen detection on intact human bone marrow (BM) colonies grown in agar layers is described. The reliability of this method allowed a study of antigenic changes during myelomonocytic differentiation. Phenotypic analysis was carried out at different times using the following monoclon...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract:OBJECTIVE:Bone marrow contains a subset of stem cells that give rise to nonhematopoietic lineages. These nonhematopoietic stem cells appear heterogeneous and contain cells committed to mesenchymal and endothelial lineages, as well as more primitive multipotential cells resembling progenitors of germ cells and very smal...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.05.014
更新日期:2009-09-01 00:00:00
abstract::High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.03.001
更新日期:2009-06-01 00:00:00
abstract::Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00680-9
更新日期:2001-04-01 00:00:00
abstract::Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although ident...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.08.003
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:To investigate whether Flk1(+)CD31(-)CD34(-) cells isolated from fetal bone marrow (BM) have characteristics of hemangioblasts, i.e., progenitors of endothelial and hematopoietic cells. MATERIALS AND METHODS:Mononuclear cells from fetal BM were negatively sorted by CD45, GlyA, and CD34 micromagnetic beads, t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00087-0
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVE:High-dose radiation exposure induces acute myeloid leukemia (AML) in C3H mice, most of which have a frequent hemizygous deletion around the D2Mit15 marker on chromosome 2. This region includes PU.1, a critical candidate gene for initiation of leukemogenesis. To identify novel cooperative genes with PU.1, rele...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.01.015
更新日期:2008-07-01 00:00:00
abstract::Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
abstract:OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.005
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current E...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.exphem.2007.08.030
更新日期:2008-02-01 00:00:00
abstract::Details are given of response and toxicity after high dose chemotherapy followed by autologous bone marrow infusion. High dose nitrosurea therapy (600-1000 mg/m2 BCNU) was predominantly associated with hematopoietic toxicity but recovery was within 4-5 weeks after BCNU therapy. High dose combination chemotherapy using...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract:OBJECTIVE:To determine the response of bone marrow progenitor cells from patients with myelodysplastic syndromes (MDS) to culture in physiologic oxygen tension. METHODS:Methylcellulose progenitor assays using both unfractionated bone marrow mononuclear cells (MNCs) and purified CD34(+) progenitors were performed in at...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.08.017
更新日期:2007-01-01 00:00:00
abstract::Human bone marrow contains plastic-adherent hemopoietic progenitor cells whose plating efficiency is increased by brief (2 h) exposure to methylprednisolone (MP). When subsequently covered with methylcellulose medium, they form colonies of monoblastoid cells. Colony size, but not number, and mature cell production are...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Marrow from Sl/Sld mice (in which the hemopoietic stromal microenvironment is defective), when implanted beneath the renal capsule of a normal littermate, produces an ectopic marrow site containing the same number of stem cells (CFU-S) and nearly as many GM-CFC as that obtained by implanting marrow from a normal litte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract:OBJECTIVE:We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MA...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)01023-8
更新日期:2003-02-01 00:00:00
abstract::A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVE:Osteoblasts play an important role in regulating hematopoiesis in the bone marrow. Here we show that U2-OS, a widely used osteoblastic cell line derived from an osteosarcoma, has the capacity to support proliferation of human hematopoietic progenitor cells in vitro. In this study, U2-OS cells are characterize...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00127-2
更新日期:2000-04-01 00:00:00
abstract::Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::We performed the present study to define the in vitro hemopoietic activity of murine recombinant (r) granulocyte colony-stimulating factor (G-CSF) using murine hemopoietic culture systems of normal bone marrow cells, fetal liver cells, and spleen cells of 5-fluorouracil (FU)-treated mice. Recombinant G-CSF supported o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Initially described as an endogenous inhibitor of proteases, the tissue inhibitor of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is a soluble protein whose levels are increased under inflammatory conditions. We recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellula...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.07.003
更新日期:2015-11-01 00:00:00
abstract::Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00