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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of interferons (IFN)-alpha, beta 2 and -gamma in inducing megakaryocytic differentiation of blast cells from a patient with acute megakaryoblastic leukaemia (AMegL) was investigated in liquid suspension culture by the increase in CD41 and CD42b expressions using monoclonal antibodies in the APAAP technique. After six days of culture, the percentage of CD41 and CD42b positive cells increased in control cultures from 15.2% and 10.6% on day 0 to 32.0 +/- 4.3% and 22.1 +/- 2.5%, respectively. The addition of IFN-alpha significantly increased the number of CD41 and CD42b positive cells by about two to three fold compared to control cultures (p < 0.01) and by about four to six fold compared to day 0 (p < 0.001) Similarly, IFN-beta 2 induced a significant increase in CD41 and CD42b positive cells. On the other hand, IFN-gamma failed to increase the number of CD41 and CD42b positive cells in comparison to control cultures on day 6 and instead stimulated a significant increase in the number of monocytes/macrophages by about ten fold compared to control cultures in IFN-gamma-treated cultures (p < 0.001). The present results suggest that megakaryocytic differentiation of blast cells in AMegL could be induced by IFN-alpha and beta 2 and support a clinical role for them in the treatment of AMegL patients. Also, the present results showed that monocytic differentiation of blast cells in AMegL could be stimulated by IFN-gamma, supporting the multipotent stem or progenitor cell origin of the AMegL subtype of acute myelogenous leukaemia.
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PMID:Effect of recombinant human interferons in inducing differentiation of acute megakaryoblastic leukaemia blast cells. 753 11

The present study shows the effect of human interferon beta (IFN beta) on the susceptibility of highly purified cord blood CD4+ T cells to infection with the human T cell leukaemia virus type I (HTLV-I). Unfractionated cord blood mononuclear cells (CBMC), or a separated CD4+ T cell subpopulation (CBCD4) were exposed to HTLV-I by cocultivation with a chronically infected virus-donor cell line. The results show that presence of proviral DNA as well as virus transcription was markedly reduced by IFN beta in both populations, indicating that this cytokine protects not only unfractionated CBMC but also purified CBCD4 cells from virus infection. Moreover IFN beta treatment caused 60%-80% inhibition of virus expression in CBCD4, assayed as the presence of virus core protein p19. This study demonstrates that IFN beta is able to inhibit HTLV-I infection of CBMC through a mechanism that does not necessarily involve cell-mediated natural or antigen-dependent immunity afforded by CBMC subpopulations distinct from targets of HTLV-I infection. Therefore it is reasonable to conclude that IFN beta has a direct protective effect on CBCD4, through induction of antiviral resistance/activity in target cells.
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PMID:Protective effect of interferon beta on human T cell leukaemia virus type I infection of CD4+ T cells isolated from human cord blood. 810 Apr 86

The production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated human leukemia T cell lines was significantly increased by 6 different cytokines. The most effective cytokines were interleukin-1 alpha (IL-1 alpha) and IL-1 beta; less effective were interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-alpha), IFN-beta and TNF-beta. The combinations of two cytokines had synergistic or additive effects and increased IL-2 production to a greater extent than either cytokine alone. Other cytokines tested, such as IL-3, IL-4, IL-6, IL-7, IL-8 and IFN-gamma, had no effect on IL-2 production. However, a remarkable heterogeneity in sensitivity to the enhancing effects of the active cytokines was found among the IL-2-producing T cell lines studied. While IL-2 production in the most sensitive cell line, MOLT-16, was increased by all 6 active cytokines, other cell lines responded by increasing IL-2 production to stimulation with only some of the cytokines tested. The production of IL-2 in T cell line H9 was not enhanced by any of the cytokines used. These results show that several cytokines can increase IL-2 production by having a direct effect on the activated IL-2-producing T cells, but also that the outcome of the regulatory effects of individual cytokines depends considerably upon the individual IL-2-producing T cell clone.
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PMID:Enhancement of interleukin-2 (IL-2) production by 6 different cytokines: heterogeneity among IL-2 producing T cell clones. 834 81

The differentiation of HL-60, a human leukemic cell line, into monocyte-like cells (D3-HL-60 cells) is induced by 1,25-dihydroxyvitamin D3 (D3). We examined the effects of interferon (IFN) treatment of D3-HL-60 cells on the expression of cell surface antigens, the phagocytic activity for fluorescent beads, production of oxygen radicals, and intracellular growth of Legionella pneumophila. Activation of D3-HL-60 cells with IFN-gamma, Beta, and alpha for 24 h significantly increased expression of CD16, CD36, CD71, and HLA-DR antigens. IFN-gamma markedly enhanced the phagocytic activity of beads in D3-HL-60 cells. There was no significant difference in phagocytic activity between cells exposed to IFN-alpha or beta and untreated D3-HL-60 cells. IFN-alpha, beta, and gamma enhanced production of oxygen radicals, including superoxide, by D3-HL-60 cells. Superoxide production was enhanced to the greatest degree by IFN-gamma, followed by IFN-beta and then IFN-gamma. Intracellular growth of L. pneumophila in D3-HL-60 cells was inhibited by interferons (IFN-gamma > beta > gamma). Similar results were obtained in human mononuclear cells. These data indicate that interferons can act as biologic response modifiers not only in human mononuclear cells but also in differentiated leukemic cells. Our results may have implications for the development of differentiation therapy for treatment of leukemia.
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PMID:Effects of interferon-alpha, beta, and gamma on the function of differentiated leukemic HL-60 cells induced by 1,25-dihydroxyvitamin D3. 872 74

HMG I(Y) proteins bind to double-stranded A + T oligonucleotides longer than three base pairs. Such motifs form part of numerous NF-AT-binding sites of lymphokine promoters, including the interleukin 4 (IL-4) promoter. NF-AT factors share short homologous peptide sequences in their DNA-binding domain with NF-kappa B factors and bind to certain NF-kappa B sites. It has been shown that HMG I(Y) proteins enhance NF-kappa B binding to the interferon beta promoter and virus-mediated interferon beta promoter induction. We show that HMG I(Y) proteins exert an opposite effect on the DNA binding of NF-AT factors and the induction of the IL-4 promoter in T lymphocytes. Introduction of mutations into a high-affinity HMG I(Y)-binding site of the IL-4 promoter, which decreased HMG I(Y)-binding to a NF-AT-binding sequence, the Pu-bB (or P) site, distinctly increased the induction of the IL-4 promoter in Jurkat T leukemia cells. High concentrations of HMG I(Y) proteins are able to displace NF-ATp from its binding to the Pu-bB site. High HMG I(Y) concentrations are typical for Jurkat cells and peripheral blood T lymphocytes, whereas E14 T lymphoma cells and certain T helper type 2 cell clones contain relatively low HMG I(Y) concentrations. Our results indicate that HMG I(Y) proteins do not cooperate, but instead compete with NF-AT factors for the binding to DNA even though NF-AT factors share some DNA-binding to DNA even though NF-AT factors share some DNA-binding properties with NF-kB factors. This competition between HMG I(Y) and NF-AT proteins for DNA binding might be due to common contacts with minor groove nucleotides of DNA and may be one mechanism contributing to the selective IL-4 expression in certain T lymphocyte populations, such as T helper type 2 cells.
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PMID:HMG I(Y) interferes with the DNA binding of NF-AT factors and the induction of the interleukin 4 promoter in T cells. 898 8

Research in cytokine biology has grown exponentially in recent years as cytokines (often also termed growth factors) are now known to be involved in a wide range of pathological and physiological processes. Continuous human leukemia cell lines represent powerful tools to investigate these mechanisms. Most cell lines grow autonomously in standard culture media (containing fetal bovine serum) independent of externally added growth stimuli. Over the last 5-10 years a battery of myeloid leukemia-derived cell lines has been established that is constitutively dependent on the addition of cytokines to the culture. Such factor-dependent cell lines die rapidly by apoptosis when deprived of the appropriate growth factor. We determined the cytokine response profiles of 19 absolutely growth factor-dependent leukemia cell lines with myelomonocytic, erythroid or megakaryocytic phenotypes with regard to enhanced or suppressed cellular proliferation. Cells were incubated in liquid culture with optimal concentrations of various recombinant human cytokines known to have effects on the growth of hematopoietic cells. A proliferative or anti-proliferative response to these 41 cytokines was assessed by the short-term 3H-thymidine uptake assay. A proliferative response was considered as positive when the stimulation index (SI) was >2; inhibition was regarded as significant with an SI <0.5. The response profile of each cell line to these 41 cytokines was different and individual. None of the cell lines responded to one or two factors only (minimum to at least five cytokines). Proliferation of most (n = 13-17), but not of all cell lines was significantly enhanced by GM-CSF, IL-3, PIXY-321, SCF and IFN-gamma. TGF-beta1 consistently inhibited proliferation (in 11/19 cell lines). IFN-alpha, IFN-beta, TNF-alpha and TNF-beta had either stimulatory or inhibitory effects. The cell lines responding most often proliferatively (to 15-19 different cytokines) were UCSD/AML1, HU-3, TF-1 and M-07e. In summary, these factor-responsive human leukemia cell lines represent extremely useful model systems for the analysis of cytokine effects on hematopoietic cells. The cytokine response profiles of the individual cell lines provide guidelines for the selection of the appropriate cell culture for such experiments.
Leukemia 1997 May
PMID:Cytokine response profiles of human myeloid factor-dependent leukemia cell lines. 918 Feb 95

Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma. It has multiple in vitro activities, including copper transport, lipid pro- and antioxidant activity, and oxidation of ferrous ion and aromatic amines; however, its physiologic role is uncertain. Although ceruloplasmin is synthesized primarily by the liver in adult humans, production by cells of monocytic origin has been reported. We here show that IFN-gamma is a potent inducer of ceruloplasmin synthesis by monocytic cells. Activation of human monoblastic leukemia U937 cells with IFN-gamma increased the production of ceruloplasmin by at least 20-fold. The identity of the protein was confirmed by plasmin fingerprinting. IFN-gamma also increased ceruloplasmin mRNA. Induction followed a 2- to 4-h lag and was partially blocked by cycloheximide, indicating a requirement for newly synthesized factors. Ceruloplasmin induction in monocytic cells was agonist specific, as IL-1, IL-4, IL-6, IFN-alpha, IFN-beta, TNF-alpha, and LPS were completely ineffective. The induction was also cell type specific, as IFN-gamma did not induce ceruloplasmin synthesis in endothelial or smooth muscle cells. In contrast, IFN-gamma was stimulatory in other monocytic cells, including THP-1 cells and human peripheral blood monocytes, and also in HepG2 cells. Ceruloplasmin secreted by IFN-gamma-stimulated U937 cells had ferroxidase activity and was, in fact, the only secreted protein with this activity. Monocytic cell-derived ceruloplasmin may contribute to defense responses via its ferroxidase activity, which may drive iron homeostasis in a direction unfavorable to invasive organisms.
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PMID:Induction of ceruloplasmin synthesis by IFN-gamma in human monocytic cells. 925 59

Induction of hepatocyte growth factor/scatter factor (HGF/SF) may be one of the critical steps in organ regeneration, wound healing, and embryogenesis. We previously reported the production of HGF/SF from various human leukemia cell lines and a high level of the growth factor in blood and bone marrow plasma from patients with various types of leukemia. We determined here the effects of hematopoietic cytokines on HGF/SF production in human leukemia cell lines, KG-1, a myeloid cell line, and RPMI-8226, a B cell line. Interferon (IFN)-gamma remarkably stimulated HGF/SF production in both cell lines at concentrations of more than 0.1 or 1 IU/ml. IFN-alpha and IFN-beta were as effective as IFN-gamma in RPMI-8226 cells, but less than IFN-gamma in KG-1 cells. HGF/SF gene expression in KG-1 cells was also up-regulated by IFN-gamma. Granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-5 and IL-6 had no effect on HGF/SF production in the 2 leukemia cell lines. We also determined the effects of HGF/SF inducers known for human fibroblasts on the growth factor production in leukemia cells. Out of phorbol 12-myristate 13-acetate (PMA), cholera toxin, IL-1 beta, and tumor necrosis factor (TNF)-alpha, the former three were as effective as IFN-gamma in KG-1 cells, but only TNF-alpha stimulated HGF/SF production in RPMI-8226 cells, whose effect was less than those of IFN-alpha, IFN-beta, and IFN-gamma. The effect of IFN-gamma in KG-1 cells was synergistic with that of PMA. In contrast with the effect in leukemia cells, HGF/SF induction by IFN-gamma in human skin fibroblasts was much less than that by PMA or cholera toxin. These results indicated that IFN-gamma is a potent inducer of HGF/SF in human leukemia cells. This finding suggests the presence of a homeostatic control mechanism in liver regeneration and repair: hepatic injury, DNA synthesis inhibition, or apoptosis caused by IFN-gamma is subsequently overcome by cytokine-induced HGF/SF, a potent promoter of liver DNA synthesis.
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PMID:Induction of hepatocyte growth factor/scatter factor by interferon-gamma in human leukemia cells. 939 61

Oromucosal administration of murine interferon-alpha/beta (IFN-alpha/beta) or individual recombinant species of murine IFN-alpha, IFN-beta, or IFN-gamma or recombinant human IFN-alpha1-8, which is active in the mouse, exerted a marked antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), or varicella zoster virus (VZV). The effects observed were dose dependent and similar in magnitude to those observed following parenteral administration of the same dose of IFN. No antiviral activity was observed after oromucosal administration of murine IFN-alpha/beta in animals in which the IFN receptor had been inactivated by homologous recombination. In contrast to parenteral treatment, oromucosal IFN therapy was found to be ineffective when IFNs were administered before virus infection. Oromucosal administration of IFN-alpha also exerted a marked antitumor activity in mice injected i.v. with highly malignant Friend erythroleukemia cells or other transplantable tumors, such as L1210 leukemia, which has no known viral etiology, the EL4 tumor, or the highly metastatic B16 melanoma. These results show that high doses of IFN can be administered by the oromucosal route apparently without ill effect, raising the possibility that the oromucosal route will prove to be an effective means of administering high doses of IFN that are clinically effective but poorly tolerated.
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PMID:Oromucosal interferon therapy: marked antiviral and antitumor activity. 1009 Apr

The scaffold attachment region of the human interferon beta gene (IFN-SAR) inserted into a retroviral vector improved transgene expression in human primary CD4+ and CD8+ T cells, and in primary monocytemacrophages. In T cells, expression of the Maloney murine leukemia virus (Mo-MuLV)-based retroviral vectors was high in activated cells but low in resting cells. Addition of the IFN-SAR sequence enhanced vector expression 2- to 10-fold, and the effect was particularly pronounced in resting T cells. In CD33+CD14+CD4+ monocyte-macrophages derived from transduced hematopoietic stem/progenitor cells (HSPCs) in vitro, the IFN-SAR enhanced vector expression three- to sixfold. We have used the IFN-SAR-containing vectors to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) rev gene. Compared with a standard retroviral vector, the IFN-SAR-containing vector was significantly (p < 0.01) more potent at inhibiting HIV-1 replication in infected CD4+ peripheral blood lymphocytes. In monocytes, however, addition of the IFN-SAR did not significantly improve antiviral efficacy. To understand better the reason for the strong effect of the SAR on antiviral efficacy in T cells we have studied the expression of HIV, Mo-MuLV, and Mo-MuLV + SAR vectors in resting and activated cells. While the expression of all three vectors was lower in resting compared with activated cells, the kinetics of the decrease in expression were fastest for the Mo-MuLV vector, followed by the HIV vector and then the Mo-MuLV + SAR vector. Thus, higher level expression of the Mo-MuLV + SAR vector relative to wild-type HIV at all stages of T cell activation is the most likely explanation for the strong antiviral efficacy. Overall, this study demonstrates the utility of the IFN-SAR sequence for achieving high-level retroviral vector expression in lymphoid and myeloid hematopoietic cells.
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PMID:Effect of scaffold attachment region on transgene expression in retrovirus vector-transduced primary T cells and macrophages. 1036 68


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