Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cell line, designated SEM, was established from the peripheral blood of a 5-year-old girl in relapse with acute lymphoblastic leukaemia (ALL). Both the lymphoblasts of the patient and the cells of the cell line SEM showed the t(4;11) chromosomal rearrangement. The analysis of the immunophenotype of the SEM cell line revealed the B-cell differentiation antigens CD19, CD22 and CDw75 in the absence of CD20, CD24 and immunoglobulin expression. Besides B-lineage antigens, SEM cells were positive for the myeloid antigens CD13, CD15, CD33 and CDw65. Immunogenotypic analysis of SEM cells showed a monoclonal rearrangement of immunoglobulin heavy-chain (IgH). T-cell receptor (TCR) gamma and delta genes. Addition of interleukin (IL)-7 promoted the growth of the patient's lymphoblasts in culture and enhanced the proliferation of SEM cells. The SEM cells also express messenger RNA (mRNA) for the IL-7 receptor (IL-7R), but no evidence for autocrine production of IL-7 by the cell line was found. Addition of IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, or IFN-gamma resulted in a profound inhibition of SEM growth. Thus, these cytokines may have important growth regulatory activities for biphenotypic leukaemic ALL cells.
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PMID:The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7. 819 15

TNF, a primary mediator of the response to infection, can be injurious to the organism when present in excessive quantities. Circulating soluble TNF receptors (sTNFR) appear to represent a natural mechanism that protects against circulating TNF. Two soluble TNF receptors (sTNFR-P55 and sTNFR-P75) circulate in vivo and are up-regulated in response to endotoxin. In this study, we investigated the kinetics of LPS-induced sTNFR release and the role of the cytokines TNF, leukemia inhibiting factor, IFN-gamma, and IL-1 in this process. The results show that LPS injection results in a rapid increase in levels of both sTNFR. Although sTNFR-P55 decreases after a peak at 30 min, sTNFR-P75 levels show a peak after 4 to 8 h, after which they slowly diminish. Both human TNF and murine TNF are capable of increasing levels of both sTNFR. Blocking circulating TNF by administration of 3 different anti-TNF agents before LPS injection (mAb to murine TNF, sTNFR55-Fc or sTNFR75-Fc) results in a significant increase of sTNFR-P55 levels, whereas only both sTNFR-Fc constructs also significantly increase sTNFR-P75 levels. Although IL-1 receptor antagonist pretreatment before LPS has no effect on TNF or sTNFR levels, leukemia inhibiting factor pretreatment significantly increases sTNFR-P55 levels. Pretreatment with anti IFN-gamma mAb before LPS results in a significant reduction in TNF and sTNFR-P55 levels, but sTNFR-P75 levels are significantly increased. Our data show that both sTNFR can be up-regulated by LPS and TNF. The influence of TNF, leukemia inhibiting factor, IL-1, and IFN-gamma on the kinetics of LPS-induced circulating sTNFR is discussed in the context of the pathophysiology of LPS-induced disease.
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PMID:LPS-induced sTNF-receptor release in vivo in a murine model. Investigation of the role of tumor necrosis factor, IL-1, leukemia inhibiting factor, and IFN-gamma. 822 46

T cell-mediated production of IFN-gamma followed infection of adult, but not neonatal NFS/N mice with Cas-Br-M murine leukemia virus (Cas). The IFN-gamma response was associated with the appearance of CTL specific for Cas and with age-dependent resistance to neurologic disease. While both immune responses were mediated by a CD8-enriched population of T cells, IFN-gamma did not play a role in the activation of the Cas-specific CTL response. However, when given exogenously, IFN-gamma delayed the onset and reduced the incidence of Cas-induced neurologic disease. These data suggest that the IFN-gamma response to Cas infection may be an important host defense mechanism whose effects on virus replication and neurologic disease expression are independent of its effect on Cas-specific CTL.
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PMID:IFN-gamma production in response to neuropathogenic Cas-Br-M murine leukemia virus infection. 829 27

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

Type I (alpha/beta) and type II (gamma) IFN enhance MHC class I gene expression through an IFN-responsive element (IRE) present in the 5' flanking region of the class I-a genes. Comparison of the 5' sequences between classical class I-a genes and T region class I-b genes reveals little homology except for presence of a potential IRE. We have found that cell surface expression of thymus leukemia Ag (TL) was up-regulated by IFN-gamma to a greater extent than H-2K,D in all TL+ T cell lines tested. In contrast, IFN-alpha/beta, which significantly increased H-2K and H-2D Ag expression, had only minor effects on TL expression. Resting peripheral T cells, which were considered to be TL- from previous studies, were found to express TL at a low level as determined by flow cytometry, immunoprecipitation, as well as polymerase chain reaction; the level of expression also could be elevated by IFN-gamma. To examine the control of TL gene transcription and its regulation by IFN-gamma, varying lengths of the T18d 5' flanking region were analyzed in chloramphenicol acetyl transferase assays. By deletion analysis, promoter activity and IFN-gamma responsiveness were localized to an 86-bp fragment that contains the IRE. Both responses were localized further to a 32-bp fragment that contained the IRE at its 3' end. RNase protection assays revealed two major transcription initiation sites, one immediately 5' of the IRE and another approximately 60 bp downstream. Furthermore, polymerase chain reaction analysis of mRNA from resting T cells, thymocytes, and T cell tumor lines confirmed the RNase protection data. Thus, transcription of T18d initiates much further upstream than the classical class I genes, can utilize an unusual promoter element, and can be elevated by IFN-gamma.
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PMID:Regulation of TL antigen expression. Analysis of the T18d promoter region and responses to IFN-gamma. 836 Apr 84

The properties of human CD45RA and CD45R0 T cells are described. CD45R0 cells respond to recall antigens and provide help for B lymphocytes. They produce a wide variety of cytokines including IL-2, IL-4 and IFN-gamma. CD45RA T cells respond poorly to recall antigens and produce mainly IL-2. The phenotype of CD45R0 cells suggests that they may be in cycle and in vivo data shows that they have a short lifespan while CD45RA cells are long lived. The lineage relationship of the two subsets is not clear but in vivo and in vitro evidence suggests bidirectional conversion between CD45RA and CD45R0 phenotypes.
Leukemia 1993 Aug
PMID:Memory and the lifespan of human T lymphocytes. 836 Dec 33

Secretion of the potentially antileukaemic cytokines IFN-gamma and TNF-alpha was investigated for CD4+ and CD8+ TCR alpha beta + T-cell clones derived from 4 leukaemia patients 3-6 weeks after allogeneic BMT. We investigated cytokine secretion in response to the activation signal accessory cells+phytohaemagglutinin+Interleukin 2. All clones derived after BMT were capable of IFN-gamma and TNF-alpha secretion, and both for CD4+ (n = 96) and CD8+ (n = 8) T cells quantities of IFN-gamma and TNF-alpha were significantly correlated with one another. When comparing the overall results for posttransplant and normal T-cell clones derived from 2 bone marrow donors (n = 65), both CD4+ and CD8+ TCR alpha beta + T-cell clones showed increased IFN-gamma production, and CD4+ but not CD8+ clones showed a decreased TNF-alpha secretion. The results suggest that noncytotoxic T cells derived after allogeneic BMT can produce IFN-gamma and TNF-alpha and may thus be capable of mediating antileukaemic effects.
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PMID:IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation. 837 Apr 21

The expression of Fc gamma receptor III (Fc gamma RIII) on a human eosinophilic leukemia cell line, EoL-1, was examined and compared with its expression on normal blood eosinophils. Surface Fc gamma RIII expression on EoL-1 cells could be induced in vitro with a combination of dibutyryl cAMP (dbcAMP) and gamma-interferon (IFN-gamma), but not with IFN-gamma or dbcAMP alone. Pretreatment of EoL-1 cells with dbcAMP induced EoL-1 cells to express Fc gamma RIII when stimulated with IFN-gamma, but EoL-1 cells pretreated with IFN-gamma and then stimulated with dbcAMP failed to express Fc gamma RIII. Cyclic AMP was shown to play a role in the effect of dbcAMP. Both the treatment with phosphatidyl-inositol-specific phospholipase C (PI-PLC) and the restriction enzyme digestion of Fc gamma RIII cDNA showed that the Fc gamma RIII on EoL-1 cells was a phosphatidylinositol-linked form. On the other hand, freshly isolated blood eosinophils constitutively expressed few, if any, Fc gamma RIII, and IFN-gamma induced Fc gamma RIII expression on them in vitro. Dibutyryl cAMP did not induce Fc gamma RIII expression and even suppressed the IFN-gamma-induced Fc gamma RIII expression on normal eosinophils. The EoL-1 cell line appears to be a useful in vitro model for the expression and function of the phosphatidylinositol-linked form of Fc gamma RIII on eosinophils.
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PMID:Induction of phosphatidylinositol-linked Fc gamma receptor III expression on an eosinophilic cell line, EoL-1, by dibutyryl cyclic AMP and interferon-gamma. 839 82

We studied the regulatory effects of various cytokines on the susceptibility to lymphocyte-mediated lysis of cell lines established from patients with acute T-lymphoblastic leukemia (T-ALL). None of the cytokines tested affected the sensitivity of these targets to natural killer activity. In contrast, specific cytokines, different for each cell line, enhanced the susceptibility to lymphokine-activated killer (LAK) cells, while interferon gamma (IFN)-gamma always induced resistance. The same cytokines that increased LAK susceptibility also induced proliferative responses. The TALL-101 cell line, which responded to granulocyte-macrophage colony-stimulating factor (GM-CSF) with increased susceptibility to lysis, and to IFN-gamma with resistance, was used as a model to analyze the mechanisms underlying these changes. Cold target inhibition and conjugate formation assays both indicated that the changes in LAK susceptibility were not at the level of effector-target (E/T) binding. Furthermore, no significant changes in surface expression of adhesion molecules involved in E/T binding were induced by either GM-CSF or IFN-gamma on TALL-101 cells. Finally, N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl-esterase assays demonstrated no differences in the ability of these cytokines to trigger the secretion of cytolysins in the bound effectors compared to unstimulated cells. Taken together, these results suggest that the cytokine-modulated susceptibility to lysis of these T-ALL lines might occur at a post-binding stage with mechanisms involving an altered responsiveness to lytic factors.
Leukemia 1993 Mar
PMID:Cytokine modulation of the susceptibility of acute T-lymphoblastic leukemia cell lines to LAK activity. 844 46

Human eosinophilic leukemia (Eol-1) cells were examined for their ability to generate platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) (PAF) and the effect of supplementation of docosa-hexaenoic acid (C22:6n-3) (DHA) on the PAF synthesis was explored in relation to the fatty acid composition of phospholipids and the liberation of arachidonic acid (C20:4n-6 AA). Although undifferentiated cells did not produce PAF, the exposure of IFN-gamma differentiated Eol-1 to generate PAF in response to the Ca-ionophore. In addition, the IFN-gamma-treated cells acquired the ability to release free fatty acids, approximately 55% of which was found to be AA. When DHA was supplemented into the culture of Eol-1 for 24 h, PAF production decreased by 40 to 50% at concentrations of 3 to 10 microM. On the other hand, supplementation of 10 microM eicosapentaenoic acid (C20:5n-3) did not significantly decrease PAF production. With the supplementation of 10 microM DHA, DHA levels in phospholipid subclasses, including alkylacylglycerophosphocholine, were greatly increased with concurrent decreases in other unsaturated fatty acids. In these cells, the liberation of AA in response to an ionophore was decreased by 55%. Even when DHA was enriched in phospholipids, DHA release in response to ionophore stimulation was almost negligible, indicating that the DHA moiety of phospholipids is not susceptible to the action of phospholipase A2. Furthermore, DHA supplementation appeared to attenuate phospholipase A2 reaction by some unknown mechanism because the decrease in AA release was much more than that for the AA level in phospholipids. Acetyl-CoA:1-alkylGPC acetyltransferase activity of stimulated cell lysate was also reduced by DHA supplementation but the reduction was much less when compared with that of PAF synthesis or AA release. These results implicated that enrichment of DHA attenuates enzymic reactions for PAF synthesis, mainly the initial reaction catalyzed by AA-specific phospholipase, and thereby reduces PAF synthesis in Eol-1.
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PMID:Effect of docosahexaenoic acid on the generation of platelet-activating factor by eosinophilic leukemia cells, Eol-1. 846 86


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