Abstract:
OBJECTIVE:All-trans retinoic acid (ATRA) has been used as the first-line therapy for patients with acute promyelocytic leukemia (APL). We previously reported that ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis during ATRA therapy for APL. In this study, we investigated the mechanism of transcriptional regulation of TPO gene by ATRA using human bone marrow stromal cells. PATIENTS AND METHODS:Real time reverse transcriptase polymerase chain reaction and Western blotting were performed to quantify TPO mRNA and protein levels in cells from the human bone marrow stromal cell line KM101. Luciferase-based reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assay were performed to identify a retinoic acid responsive element in the promoter region of TPO gene (TPO-RARE). RESULTS:TPO mRNA expression was up-regulated by approximately 2.9 times 8 hours after stimulation with 10(-6) M ATRA in KM101 cells. In contrast, ATRA did not alter TPO mRNA expression in cells from the human hepatoma cell line HepG2. Protein level of KM101 cells also was increased with 10(-6) M ATRA for 48 hours in KM101 cells. We found the synthesized RARalpha protein bound to [gamma-32P]-labeled TPO-RARE probe and its binding was competed by adding 200x amount of cold TPO-RARE probe by EMSA. In addition, [gamma-32P]-labeled TPO-RARE probe bound to KM101 nuclear protein extract was supershifted by anti-RARalpha antibody and modified by treatment with ATRA. The relative luciferase activity of TPO gene was increased by 2.2x and the histone H4 was acetylated through TPO-RARE after ATRA stimulation in KM101 cells by ChIP assay. CONCLUSION:These data support the direct up-regulation of TPO transcription by ATRA stimulation in human bone marrow stromal cells and propose one of the mechanisms of thrombocytosis during ATRA therapy for APL.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kinjo K,Miyakawa Y,Uchida H,Kitajima S,Ikeda Y,Kizaki Mdoi
10.1016/j.exphem.2003.10.009keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
45-51issue
1eissn
0301-472Xissn
1873-2399pii
S0301472X03003503journal_volume
32pub_type
杂志文章abstract::Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone mar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Normal and myeloid leukemic spleen cells from RF mice were cultured in vitro in plasma clots. In situ histochemical staining and karyotypic analysis of the colonies formed in the clot revealed that the colonies produced by leukemic and normal progenitors were indistinguishable morphologically and cytochemically. Colon...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::The reproducibility and utility of an in vitro bioassay for erythropoietin were evaluated, and modifications, including the use of frozen target cells, were made. The assay, based on 3H-thymidine incorporation into phenylhydrazine-treated mouse spleen cells, showed a dose-response curve from 0.2 to 20 mU of sheep plas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract:OBJECTIVE:MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that regulate diverse cellular functions by sequence-specific inhibition of gene expression. We determined miRNA expression profile during erythroid differentiation and putative roles in erythroid differentiation. METHODS:The expression profile...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.03.014
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:alpha4 Integrins are major players in lymphoid cell trafficking and immune responses. However, their importance in lymphoid reconstitution and function, studied by antibody blockade or in genetic models of chimeric animals with alpha4(KO) embryonic stem (ES) cells, competitive repopulation experiments with fe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.03.008
更新日期:2008-08-01 00:00:00
abstract::Embryonic and adult stem cell populations have great potential value in medicine, and hematopoietic stem cells are already being used in transplantation. Definition of these populations to increase our understanding of the programs that control differentiation, self-renewal, and possibly plasticity would be of great i...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2003.08.012
更新日期:2003-12-01 00:00:00
abstract::After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the developm...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.09.006
更新日期:2019-01-01 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::The advent of single-cell transcriptomics has led to the proposal of a number of novel high-resolution models for the hematopoietic system. Testing the predictions generated by such models requires cell fate potential assays of matching, single-cell resolution. Here we detail the development of an in vitro high-throug...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.01.005
更新日期:2018-04-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 00:00:00
abstract::Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synth...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00054-x
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVE:The ABCG2 transporter has been identified as a determinant of the side population (SP) in murine bone marrow and a potential marker for primitive stem cells. To assess the potential of the SP phenotype and ABCG2 expression to identify stem cells in human umbilical cord blood (hUCB), we have examined directly ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.09.015
更新日期:2009-02-01 00:00:00
abstract::Media conditioned by B-lymphocytes of patients with chronic lymphocytic leukemia (B-CLL) induced the formation of multilineage colonies (CFU-GEMM) in cultures of human target marrow cells. Maximum levels of stem cell colony-stimulating activity (CFU-GEMMCSA) were detected by day 3 of leukemic B-cell cultures, remainin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract:OBJECTIVE:Our laboratory reported that the angiotensin converting enzyme inhibitor captopril improves erythroid recovery from total body irradiation (TBI) in mice when administered after irradiation. However, captopril administered before TBI attenuates erythroid recovery. Here we investigate captopril and radiation re...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.12.002
更新日期:2011-03-01 00:00:00
abstract::Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific poly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.11.005
更新日期:2014-03-01 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::Epitopes on the CD34 molecule detected by some CD34 antibodies can be cleaved by a unique glycoprotease from Pasteurella haemolytica, which cleaves only glycoproteins rich in O-linked glycans. A method to isolate CD34+ cells from adult bone marrow was developed subsequently, in which CD34+ cells were isolated in high ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::The effects of intraperitoneal Ehrlich ascites tumor (ET) growth on the kinetics of hemopoietic stem cells in the host bone marrow were studied using the spleen colony and the soft agar culture techniques. There is a decrease in spleen colony forming capacity of bone marrow of ET bearing mice, whereas in vitro assays ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-05-01 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:OBJECTIVE:A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS:The HSC activity of porcine c-kit+ BMCs was ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00197-8
更新日期:2003-09-01 00:00:00
abstract::In slightly more than a decade of stem cell plasticity research, 24 peer-reviewed articles have demonstrated plasticity across organ and/or embryonic lineage boundaries at the single-cell level, with only 1 article showing negative results. These data, taken together with data about reversibility of gene restrictions ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2010.04.013
更新日期:2010-07-01 00:00:00
abstract::Erythropoiesis requires large amounts of iron for hemoglobin synthesis. There are two sources of iron for erythropoiesis, dietary and stored iron; however, their relative contributions to erythropoiesis remain unknown. In this study, we used the stable iron isotope (57)Fe to quantify synthesis of hemoglobin derived fr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.02.005
更新日期:2016-06-01 00:00:00
abstract::The production of interferon-alpha (IFN-alpha) by normal human peripheral blood mononuclear cells (PBMNC) was studied using polyclonal antipeptide antibodies designed to react either with all IFN-alpha subtypes or with individual subtypes IFN-alpha 2 or IFN-alpha 4. In this study, we demonstrate the detection of intra...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Nasal natural killer-T cell lymphoma (NNKTL) is associated with the Epstein-Barr virus and has distinct histologic features, such as angiocentric and polymorphous lymphoreticular infiltrates that contain too many cell types, including tumor and inflammatory cells. We have shown previously that intercellular adhesion m...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.03.009
更新日期:2013-08-01 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::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::Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, C...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00