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 previously established subclones from human leukemia-derived HSB.2 cell line that produced high levels of interleukin (IL) 2 when stimulated with phytohemagglutinin (PHA) and IL-1. Herein, we investigated the signal requirement for IL-2 production, particularly concerning the role of IL-1 in this system. PHA but not IL-1 rendered marked protein kinase C (PKC) activation and IL-2 production induced by PHA plus IL-1 was totally abrogated by a potent PKC inhibitor, H-7. Concomitantly, PHA alone caused marked Ca2+ influx, whereas IL-1 neither induced Ca2+ influx nor augmented PHA-induced Ca2+ influx. As expected, a signal delivered by PHA could be substituted by phorbol 12-myristate 13-acetate (PMA) and ionomycin while IL-1 was still indispensable, indicating that at least three signals, i.e., those delivered by IL-1 as well as PKC activation and Ca2+ influx were required for optimal IL-2 production. Kinetic study indicated that while PMA and ionomycin should be added at the initiation of culture, delayed addition of IL-1 up to 4 hr later induced even higher levels of IL-2 production, demonstrating the requirement for IL-1 after PKC activation and Ca2+ influx. In this system, it was revealed that IL-1 was not involved in PKC activation, Ca2+ influx, and breakdown of phosphatidylinositols. Whereas PMA, ionomycin, and IL-1 stimulated high levels of IL-2 production, those combinations of signals did not induce breakdown of phosphatidylinositols. It should be noted that IL-2 production induced by these three signals seemed to bypass hydrolysis of phosphatidylinositols in contrast to PHA plus IL-1 stimulation that was accompanied with a marked breakdown of phosphatidylinositols.
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PMID:Signal requirement for interleukin-1-dependent interleukin 2 production by a human leukemia-derived HSB.2 subclone. 350 Feb 16

We studied the presence of peripheral-blood- and bone-marrow-derived T-lymphocyte colony formation (CFU-TL) in 28 bone marrow transplant recipients from 1 month to six years after transplantation. Peripheral blood leukocyte and lymphocyte counts were generally normal, and all had morphologic evidence of engraftment without leukemia at the time of study. Both peripheral-blood- and bone-marrow-derived CFU-TL were markedly reduced after transplantation as compared to normal controls, which included bone marrow donors (14.2 +/- 5/4 X 10(4) vs 313 +/- 100/4 X 10(4) [p less than 0.001] and 26 +/- 4/2 X 10(5) vs 1004 +/- 60/2 X 10(5) [p less than 0.001]). Among the patients, four had no detectable bone-marrow-derived CFU-TL when tested less than six months after transplantation. Peripheral blood CFU-TL, while present in all patients, was markedly decreased for more than 12 months after transplantation. After two years, the number of CFU-TL returned to normal in several patients. The abnormalities in CFU-TL were unrelated to diagnosis, age, sex, graft-versus-host disease (GVHD), pretransplant conditioning, or posttransplant immunosuppressive treatment. Patients receiving autologous bone marrow transplants also had decreased CFU-TL. Cocultures of normal peripheral-blood- or bone-marrow-derived mononuclear cells with recipients' mononuclear cells or sera did not inhibit normal CFU-TL growth. Furthermore, the addition of mononuclear cells or sera from normal individuals, or of exogenous interleukin 1 or interleukin 2, did not correct the deficiency of CFU-TL growth by recipient cells. Depletion of T-lymphocytes from bone marrow or peripheral blood in transplant recipients by physical techniques or with a monoclonal antibody (CT-2) and complement had no effect on CFU-TL recovery. Similarly, addition of recipients' T cells to normal peripheral blood or bone marrow mononuclear cells did not suppress CFU-TL. These data indicate that most transplant recipients have a marked reduction in CFU-TL which persists for up to two years after transplantation. This reduction in the growth of T-cell colonies appears to be due to deficient numbers of these cells or an intrinsic defect in their responsiveness to T-cell lymphokines, rather than a result of growth suppression by inhibitory cells or serum factors. This observed defect in CFU-TL may have implications for therapeutic attempts to facilitate immune reconstitution after bone marrow transplantation.
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PMID:Abnormal T-lymphocyte colonies (CFU-TL) following bone marrow transplantation. 353 45

Leukemia cell lines of the monocytic series (HL-60, U-937, and P388D1) produce a hepatocyte-stimulating factor (HSF) following induction of differentiation with phorbol diester. In 24-72 hr, these leukemia cells produce 2-30% the amount of HSF as human peripheral blood monocytes. Cells of the series at earlier stages of differentiation produced greater amounts of HSF. Fractionation of the medium from each cell type by HPLC reveals much of the HSF activity in the 25- to 30-kilodalton range. Under the same culture conditions, interleukin 1 is produced; however, its bioactivity is in the 7- to 15-kilodalton range. Neither monokine shows reciprocal bioactivity. Superinducing culture conditions that greatly increase interleukin 1 production completely eliminate HSF production, suggesting that there is different stability of the mRNA coding for each protein or that there are different temporal events important to the induction of synthesis of these proteins.
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PMID:Identification and partial characterization of hepatocyte-stimulating factor from leukemia cell lines: comparison with interleukin 1. 388 60

Immunosuppression is commonly associated with retrovirus-induced animal tumors. Studies in the murine and feline retrovirus systems suggest that the 15,000-dalton envelope protein (p15E) of the virion may contribute to immunosuppression by interfering with normal lymphocyte function. We examined the effect of inactivated feline leukemia virus (UV-FeLV) and p15E derived from this virus on concanavalin A (Con A) driven human T cell proliferation. Virus and p15E markedly suppressed mononuclear cell proliferative response to Con A. Suppression was not due to inhibition of monocyte accessory cell function, or interleukin 1 (IL 1) secretion. In fact, the presence of monocytes partially protected T cells from UV-FeLV suppression. UV-FeLV, however, suppressed T cell secretion of and response to interleukin 2 (IL 2). We conclude that UV-FeLV and derived p15E inhibit T cell proliferation by direct inhibition of T cell function. These findings, extended to the in vivo situations, suggest that retrovirus-associated suppression of the immune response involves the induction of T cell but not monocyte dysfunction.
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PMID:The mechanism of retrovirus suppression of human T cell proliferation in vitro. 631 4

The SPI-802 human leukemia cell line, which possesses E receptors and used to have natural killer activity, has been demonstrated to produce high levels of interleukin 1 (IL-1)-like activity. SPI-802 supernatants prepared in 1% serum-containing cultures with lipopolysaccharide stimulation, like similarly prepared adherent-cell-derived IL-1, enhanced phytohemagglutinin-induced mouse thymocyte proliferation. When adherent-cell IL-1 gave 50% maximum activity at a reciprocal dilution of 20, SPI-802 supernatant gave it at 200, indicating the production of high levels of IL-1-like activity by the cell line. SPI-802 supernatant promoted the production of interleukin 2 (IL-2) by the Jurkat-F1884 T-cell line: Levels of IL-2 activity obtained with 15% SPI-802 supernatant were almost equivalent to those obtained with 50% adherent-cell IL-1 as estimated by the maximum proliferation of IL-2-dependent cytotoxic T cells. SPI-802 supernatant by itself exhibited no IL-2 activity. Major IL-1-like activity of SPI-802 supernatant was present in fractions from AcA54 columns corresponding to Mr 12,000-20,000 and 60,000-70,000 and resolved on isoelectrofocusing into two distinct species with pI values of 5.0 and 7.0, being consistent with the results of adherent-cell IL-1. The SPI-802 cell line having E receptors is an ideal source of a soluble factor with the biological and biochemical characteristics of human IL-1.
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PMID:Production of high levels of interleukin 1-like activity by the SPI-802 human leukemia cell line with E receptors. 633 84

Antibodies with specificity for interleukin 1 (IL 1) were produced in a goat immunized with purified IL 1 alpha obtained from the murine macrophage cell line, P388D1. The anti-IL 1 IgG were capable of completely inhibiting the biologic activity of IL 1 in the murine thymocyte assay but had no effect on IL 2-driven T cell responses. Although the anti-IL 1 IgG were produced by using mouse IL 1, these antibodies also recognized IL 1 prepared from a human monocyte leukemia cell line. An immunoadsorbent column was prepared and used for the large-scale purification of IL 1 in relatively high yield. Approximately 250 micrograms of purified IL 1 were obtained from 50 liters of culture fluid, the yield being 20% of the initial activity. Six major species of IL 1 were resolved by using tris-glycinate discontinuous polyacrylamide gels. The purified IL 1 exhibited 50% of its maximal activity in the thymocyte proliferation assay at a concentration of approximately 1 X 10(-11) M.
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PMID:Preparation of goat antibodies against interleukin 1: use of an immunoadsorbent to purify interleukin 1. 635 5

It is shown that the anti-trinitrophenyl (TNP) response of human B cells to trinitrophenyl polyacrylamide beads (TNP-PAA) is monocyte dependent. This response is abolished by extensive adherent cell depletion and restored by the addition of monocytes. The optimal response is obtained with 3% monocytes, higher numbers being suppressive. Supernatants from muramyl dipeptide (MDP)-activated monocytes can restore the response of monocyte-depleted preparations even when cells are cultured at suboptimal concentration. A partially purified preparation of interleukin (IL-1) has a comparable restorative ability. The following arguments suggest that monocytes do not function as antigen-presenting cells for this particulate antigen: (i) antigen-pulsed monocytes induce neither an anti-TNP response nor a specific T-cell proliferative response; (ii) allogeneic monocytes function as well as autologous monocytes to restore the response of nonadherent cells; (iii) HLA-DR-negative cells from the human leukemia cell line K562 can replace monocytes for this response. Monocyte supernatants do not replace T cells for the response of B-enriched lymphocytes, showing that T cells are directly involved in B-cell activation.
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PMID:Interleukin 1 can replace monocytes for the specific human B-cell response to a particulate antigen. 661 Apr 77

A murine leukemia subline (L17R) was selectively developed in the presence of conditioned medium of a thymic reticuloepithelial-like cell line (B6TE). Cytotoxicity tests and immunofluorescence microscopy showed that L17R cells were negative in the expression of Thy 1.1, Lyt 1.2 and terminal deoxynucleotidyl transferase (TdT), however, 35% positive in Lyt 2.1 phenotype, and 95% positive in the expression of peanut agglutinin (PNA) receptor. B6TE conditioned medium had no activity of interleukin 1 (IL 1), interleukin 2 (IL 2), interleukin 3 (IL 3) and granulocyte/macrophage colony-stimulating factor (GM-CSF). When L17R leukemic cells were plated at a low cell density, their growth was accelerated 40 times by the addition of concentrated B6TE culture supernatant. This growth activity, tentatively designated leukemia-growth-promoting factor (LGPF), was heat sensitive, and its mol. wt was estimated to be approx. 25,000 from the elution pattern of Sephadex G-100 chromatography.
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PMID:Growth of a cultured leukemia subline was promoted by conditioned medium of thymic reticuloepithelial-like cells (B6TE). 664 1

Acute myelogenous leukemia is characterized by the infinite proliferation of malignant leukemia cells and by the impaired hematopoiesis. The proliferation of leukemia cells is supported by a small subpopulation, leukemic blast progenitors. Leukemic blast progenitors make leukemic blast colonies in methylcellulose culture. To determine the mechanism by which leukemia cells proliferate, we studied the role of several cytokines in the proliferation of leukemic blast progenitors in vitro. The findings indicated that there are at least three types in the regulation by cytokines of the leukemic cell growth. One is the stimulation of leukemic blast progenitors by colony-stimulating factors(CSFs) or interleukins(ILs) added in culture. These cytokines include granulocyte-CSF(G-CSF), granulocyte-macrophage CSF (GM-CSF), IL-3 and IL-1. The second is the autocrine growth mechanism. Leukemia cells by themselves produce and secrete G-CSF and GM-CSF, which stimulate the growth of leukemic blast progenitors. The third is a complex mechanism. IL-1, produced by leukemia cells or other cells, enhances the production of GM-CSF by leukemia cells, which stimulates the growth of leukemic blast progenitors. The precise mechanism by which each cytokine acts on leukemic blast progenitors should be determined to explore the mechanism of leukemia cell growth.
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PMID:[The role of cytokines in the proliferation of leukemia cells in acute myelogenous leukemia]. 750 32

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89


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