Abstract:
:Previous studies in animal models have suggested that bone marrow-derived interleukin-2 (IL-2) activated natural killer (A-NK*) cells can be used to eliminate residual leukemic cells both in vivo and in vitro. As part of initial studies to develop a clinical protocol to exploit this phenomenon in combination with culture purging of leukemic cells, we examined a number of variables that might affect either IL-2 stimulation of natural killer (NK) cell activity or maintenance of primitive hematopoietic cells in cultures suitable for manipulating human marrow autografts. Cytotoxicity of IL-2 A-NK cells was determined using K562 and Daudi target cells in a standard 4-hour 51Cr release assay. Primitive hematopoietic cells were quantitated using both direct clonogenic progenitor assays and the long-term culture-initiating cell (LTC-IC) assay. The latter measures a very primitive cell type that gives rise to clonogenic cells after > 5 weeks of culture on pre-established marrow feeder layers. Light-density (< 1.070 g/cm3) human marrow cells cultured at 10(6) cells/mL for 7 days at 37 degrees C in the presence of 1000 U of either natural or recombinant human IL-2 showed a marked generation of A-NK cell function that was not seen if IL-2 was not added. The cytotoxicity was the same whether the cells had been maintained in standard fetal calf serum (FCS)-supplemented medium or in LTC medium (which also contains horse serum and 10(-6) M hydrocortisone) or whether adherence of cells during the culture period was promoted or prevented. The level of NK activity in IL-2-stimulated cultures of marrow cells from patients with acute myeloid leukemia (AML) in remission was not significantly different from that obtained with normal marrow. The initial numbers of clonogenic cells in these samples were close to normal values (60%). For both normal and AML patient samples, these declined slightly during the 7-day culture period, regardless of whether IL-2 was present. Starting values for LTC-IC in patient marrow samples were markedly reduced to approximately 7% of normal values, but as in normal cultures, did not decrease further in culture with or without IL-2. These results indicate that activation of bone marrow-derived NK cells can be obtained in 7-day cultures containing IL-2 under conditions that preserve the most primitive hematopoietic cells currently detectable.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Klingemann HG,Deal H,Reid D,Eaves CJsubject
Has Abstractpub_date
1993-08-01 00:00:00pages
1263-70issue
9eissn
0301-472Xissn
1873-2399journal_volume
21pub_type
杂志文章abstract::Hematopoietic stem cell transplantation (HSCT) is an established treatment for multiple myeloma (MM), a plasma cell malignancy. To identify an improved pretransplant conditioning regimen, we investigated the cytotoxicity of gemcitabine (Gem) and clofarabine (Clo) combinations toward MM cell lines and patient cell samp...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.04.009
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVE:Assays that can evaluate the potential of individual human hematopoietic stem cells (HSC) are still lacking. We previously developed the myeloid-lymphoid initiating cell (ML-IC) assay that enumerates single CD34(+) cells that generate long-term culture-initiating (LTC-IC) and NK-initiating (NK-IC) daughter ce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.10.016
更新日期:2005-02-01 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:OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.001
更新日期:2010-11-01 00:00:00
abstract:OBJECTIVE:Hemopoiesis is regulated by cytokines with positive or negative effects on proliferation of lineage-committed or multipotent hemopoietic stem cells. We have investigated the roles of interleukin-6 and other gp130-dependent ligands on the proliferation of macrophage-lineage hemopoietic progenitor cells. METHO...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00512-9
更新日期:2000-10-01 00:00:00
abstract:BACKGROUND:Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/s0301-472x(01)00732-9
更新日期:2001-11-01 00:00:00
abstract::HIV-derived lentiviral vectors have been used widely to transduce non-dividing cells, such as hematopoietic stem cells (HSCs), in the setting of gene therapy. In this study, we screened lentiviral vectors for their ability to drive expression of the murine MHC class II chaperone, invariant chain (Ii) and a GFP reporte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.07.002
更新日期:2013-11-01 00:00:00
abstract::In hematopoietic cell development, the transcriptional program is strictly regulated in a lineage- and stage-specific manner that requires a number of transcription factors to work in a cascade or in a loop, in addition to interactions with nonhematopoietic cells in the microenvironment. Disruption of the transcriptio...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.06.001
更新日期:2017-09-01 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:OBJECTIVE:Hematopoietic stem cells (enriched in fraction of CD34+ cells) have the ability to regenerate hematopoiesis in all of its lineages, and this potential is clinically used in transplanting bone marrow or peripheral blood stem cells. Our objective was to assemble a suitable method for evaluating gene expression ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.006
更新日期:2006-07-01 00:00:00
abstract::Although three molecular forms of macrophage colony-stimulating factor (M-CSF) have been reported, Western blot analysis of immunoaffinity-purified M-CSF from human blood has shown that the major species of M-CSF in the serum has a molecular weight (MW) of 85 kD. Superose-12 gel filtration chromatography of immunoaffi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:A complete process for mass generation of megakaryocytes from hematopoietic stem cells under serum-free conditions has great clinical potential for rapid platelet reconstruction in thrombocytopenia patients. We have previously reported on the generation of an optimized serum-free medium (serum-free hematopoie...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.012
更新日期:2009-11-01 00:00:00
abstract::Dendritic cells (DC) are recognized as the most potent antigen-presenting cells with the ability to stimulate naive resting T cells and to initiate primary immune responses. Encouraging results in vaccination studies in animal models and the development of protocols to generate sufficient numbers of human DC for clini...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/s0301-472x(01)00730-5
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVE:It is well known that hypoxic stress strongly enhances erythropoiesis, but the effect of hypoxia on erythroid progenitors has not been examined precisely. In the present study, using the erythropoietin-dependent cell line UT-7/Epo, which has characteristics of erythroid progenitors, we investigated a novel ro...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.01.013
更新日期:2005-05-01 00:00:00
abstract::Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutrali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::The results and complications of 224 marrow collections from 200 patients with malignant disease who underwent marrow aspiration and storage for subsequent autologous marrow transplantation (AMT) were analyzed. The median age of the patients was 35 years (range 1-68); 131 patients had hematologic malignancies and 69 h...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.030
更新日期:2007-04-01 00:00:00
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 ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00658-0
更新日期:2001-07-01 00:00:00
abstract::Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.04.010
更新日期:2017-08-01 00:00:00
abstract::Serum erythropoietin (Epo) levels are depressed in anemic AIDS patients relative to controls. The basis for abnormal regulation of Epo has not been defined. The hepatoma cell line Hep3B produces Epo in response to hypoxia and serves as a model for the study of Epo regulation. Hep3B cells are infectible with human immu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.08.003
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. METHODS:We t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.02.007
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the effect of CF101, a synthetic agonist to the A3 adenosine receptor (A3AR), on the production of granulocyte colony-stimulating factor (G-CSF). The ability of CF101 to act as a myeloprotective agent in chemotherapy-treated mice was tested. METHODS:CF101 was administere...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00962-1
更新日期:2002-12-01 00:00:00
abstract::The extent of incorporation of bromodeoxyuridine (BrdUrd) into DNA of different types of hematopoietic stem cells assayed in vivo and of progenitor cells assayed in vitro was determined after continuous infusion of BrdUrd into mice for either four or seven days. Cells surviving subsequent exposure to 320 nm ultraviole...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-10-01 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::The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:Recent reports have shown that killer immunoglobulin-like receptors (KIR) and KIR ligand (KIR-L) genotype play a role in the pathophysiology of autoimmune disorders. Certain KIR/KIR-L combinations might convey a predisposition to immune-mediated bone marrow failure. Examining the genotypic makeup of human leu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.07.005
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVE:We have previously shown that Flt3 ligand (FL)/Flt3 signaling regulates hematopoietic cell migration by modulating the SDF1alpha/CXCR4 signaling pathway. Herein, we evaluated whether a functional interaction between SDF1alpha/CXCR4 signaling and internal tandem duplication (ITD) of Flt3 regulates aberrant hem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.001
更新日期:2006-08-01 00:00:00
abstract::Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00