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)

We have examined a correlation between an expression level of poly(ADP-ribose) synthetase gene and the stage of monocytic differentiation. We selected three human leukemia cell lines, U937, THP-1, and J111, whose differentiation stage was characterized by nitroblue tetrazolium reduction activity, non-specific esterase activity, phagocytic activity and a cell surface marker. Enzyme activity and mRNA level of the synthetase decreased in accompaniment with the progress of monocytic differentiation. When THP-1 cells were treated with either interferon-gamma or phorbol ester, mRNA level of the synthetase decreased and HLA-DR or interleukin-1 was induced, respectively. We transfected expression plasmid of the exogenous synthetase gene to examine whether the down-regulation of the synthetase is a necessary step to induce these proteins. An expression of the exogenous synthetase gene inhibited the interferon-gamma- and phorbol ester-dependent induction of HLA-DR and interleukin-1. The results suggest that down-regulation of the synthetase may be a signal mediator of immunological response such as HLA-DR or interleukin-1 production in monocytes.
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PMID:Inhibition of interferon-gamma- and phorbol ester-induced HLA-DR and interleukin-1 production by the expression of a transfected poly(ADP-ribose) synthetase gene in human leukemia THP-1 cells. 131 13

A human promyelocytic leukaemia cell line, HL-60 cells, did not show accessory cell (AC) function to potentiate the proliferation of human T cells induced by anti-CD3 antibody coupled to latex beads (alpha T3-L). This was found to be at least due to the inability of HL-60 cells to express certain molecules which are inducible with interferon-gamma (IFN-gamma) on mature monocytes and are necessary for interaction with T cells. HL-60 cells acquired the ability to express such surface molecules by stimulation with IFN-gamma when the cells were pretreated with 1,25-dihydroxyvitamin D3 (Vit D). The effect of Vit D was reversible, that is, the AC function of the HL-60 cells was lost when the cells were cultured in Vit D-free medium for 7 days. It was also found that HL-60 cells treated with IFN-gamma and then with Vit D did not show significant AC function. The flow cytometric analysis showed that the expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) was highly increased on HL-60 cells when stimulated with IFN-gamma after treatment with Vit D. The expression of ICAM-1 was also induced with IFN-gamma on untreated cells but in lower amounts. Monoclonal antibodies against ICAM-1 and HLA-DR inhibited the alpha T3-L-induced T-cell proliferation, indicating that these molecules are at least required for contact-mediated AC function. Thus our study revealed that HL-60 cells express cell surface interaction molecules necessary for potentiating the T-cell proliferation through two steps, differentiation with Vit D to mature monocyte-like cells followed by stimulation with IFN-gamma.
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PMID:Development of the cell contact-mediated accessory function for T-cell proliferation in a human promyelocytic leukaemia cell line, HL-60, by 1,25-dihydroxyvitamin D3. 135 May 68

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32). 136 20

In an effort to identify unique tyrosine kinases found in human leukemia cell lines, we utilized polymerase chain reaction (PCR) technology and degenerate oligonucleotide primers to produce a cDNA library of kinase catalytic domains found in the human monocytic cell line AML-193. This search yielded a member of the class 3 tyrosine kinases closely related to the murine kinase FD-22. Previous work has identified this kinase as JAK1. This class of tyrosine kinases is characterized by being ubiquitously expressed, lacking both a ligand-binding domain and a SH2 domain, while containing a second domain similar to a degenerate kinase domain. Our studies focused on the further characterization of this class 3 tyrosine kinase using Northern blot analysis to demonstrate an increase in steady-state mRNA by interferon-gamma in human monocytes. A human-hamster somatic cell hybrid panel and linkage mapping was used to assign JAK1 (aml-116) to human chromosome 1.
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PMID:Characterization of a class 3 tyrosine kinase. 137 77

Proliferation of human leukemia cells, HL60, was synergistically inhibited by a combination of human interferons and azidothymidine in vitro. Combination of interferon-gamma (3000 U/ml) and azidothymidine (30 microM) inhibited cell growth by 76%, whereas interferon-gamma alone suppressed growth by 23% and azidothymidine alone by 33%. Interferon-alpha-2a and interferon-beta also exerted synergistic effects with azidothymidine, but the potentiation was weaker than that by the combination of interferon-gamma and aziodthymidine.
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PMID:Synergistic antiproliferative effect of interferons and azidothymidine on HL60 cells. 137 2

Astrocytes have been regarded as the matrix of the central nervous system and as nutritional, metabolic support to neurons. Recently, immunological roles of astrocytes have been reported, especially in multiple sclerosis and experimental allergic encephalitis. One observation shows that human glioma cells, which lack CD4 molecules, can be infected with human immunodeficiency virus in vitro. Another report described that human macrophages can be infected with human immunodeficiency virus through Fc gamma receptors expressed on their cell surfaces. These results prompted us to examine the functioning molecules, especially Fc gamma receptor for immunoglobulin G, expressed on the astroglial cell line. From erythrocyte-antibody rosette assays, redirected cytolysis and flow cytometric analysis, we have shown that human astrocytoma cell lines possess Fc gamma receptors on their cell surfaces. Furthermore, primary cultured murine astrocytes express Fc gamma II receptors, reacting with 2.4G2 monoclonal antibody. Surprisingly, murine astrocytes prepared from newborn BALB/c mice demonstrate killing activity against allogeneic T cell leukemia by antibody-dependent cellular cytotoxicity. After treatment with the macrophage activating factor, interferon-gamma, expression of Fc gamma receptors and killer activity of astrocytes were augmented. From these results, it is suspected that the astroglial cell lines play an important immunological role in the brain.
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PMID:Expression of Fc gamma receptors on astroglial cell lines and their role in the central nervous system. 138 16

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.
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PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. 146 94

After activation by interferon-gamma (INF-gamma) and lipopolysaccharide(LPS), mouse peritoneal macrophages were cocultured with P388 parental cell line (P388/PRT) and its adriamycin (ADM)-, cisplatin(CDDP)-, cyclophosphamide(CPM)-, and mitomycin-C(MMC)-resistant cell lines for one day at effector:target ratios (E:T) of 10:1, 5:1, and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cleavage assay and a new indirect MTT assay as well as clonogenic assay were used to quantitate activated macrophage-mediated cytotoxicity to these non-adherent leukemia targets. The results revealed that all the P388 cell lines can be suppressed efficiently by activated macrophages, but P388 CPM- and MMC-resistant cell lines (P388/CPM, P388/MMC) were more susceptible than P388/PRT while P388 ADM- and CDDP-resistant cell lines (P388/ADM, P388/CDDP) shared equal level of survival rates with P388/PRT. This study also showed that both non-activated and activated macrophages can produce formazan in a high level, which can interfere with the final results of direct MTT assay. The new indirect MTT assay can avoid such interference by separating the effectors from the targets before performing the MTT assay and reflects the real viability of the targets so the indirect MTT assay developed in this study could be a better way to examine cytostatic and cytotoxic effect of activated macrophages on non-adherent tumor cells in vitro.
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PMID:Differential macrophage-mediated cytotoxicity to P388 leukemia cells and its drug-resistant cells examined by a new MTT assay. 146 25

In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia. 151 Nov 67

To find predictive parameters for development and progression of adult T-cell leukemia (ATL) in human T-cell leukemia virus type-I (HTLV-I) carriers, we investigated cellular immune responses such as mitogenic responses and natural killer activity of the peripheral blood mononuclear cells (PBMC). And serum or plasma levels of cytokines, including tumor-necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and immunosuppressive acidic protein (IAP), were also measured in patients with ATL, healthy HTLV-I carriers and healthy HTLV-I non-carriers as controls. Results are as follows: (1) increased spontaneous proliferation and decreased mitogenic responses of PBMC already existed in HTLV-I carriers; (2) IAP was significantly higher in patients with acute/lymphoma type ATL than in those with chronic/smoldering type, HTLV-I carriers and HTLV-I non-carriers. These results suggest that spontaneous proliferation or mitogenic responses and IAP may be useful parameters for the development and progression of ATL from the carriers. Since HTLV-I carriers already have various grades of immunosuppression, we should seriously try to prevent further HTLV-I transmission.
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PMID:Immune responses and serum levels of cytokines in adult T-cell leukemia patients and human T-cell leukemia virus type-I carriers. 154 82


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