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

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Leukemia 1989 Aug
PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

Autonomous in vitro growth of myeloid leukemic colony-forming cells may in part result from autocrine production of colony-stimulating factors (CSF). Some acute myeloid leukemia (AML) samples, however, fail to synthesize CSF despite growing autonomously in agar, and are therefore believed to bypass CSF requirements. Cytokines such as IL-6, tumor necrosis factor (TNF)-alpha, and IL-1, products of cells of the myeloid lineage, are known to be involved in growth control of myeloid progenitor cells. Since these molecules may also contribute to autocrine and paracrine growth regulation of myeloid leukemias, we screened a series of AML for cytokine production. In addition, possible roles of IL-6, TNF-alpha, and IL-1 in growth control of AML were investigated in vitro. We show that a substantial proportion of AML cells produce IL-6, TNF-alpha, and IL-1-beta and use these mediators to stimulate their growth by disparate mechanisms: IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blasts. TNF-alpha induces CSF production by endothelial cells and may therefore provide a paracrine loop to support leukemia growth.
 ...
PMID:Participation of the cytokines interleukin 6, tumor necrosis factor-alpha, and interleukin 1-beta secreted by acute myelogenous leukemia blasts in autocrine and paracrine leukemia growth control. 1456 12

Bacterial products are potent stimulators of TNF and IL-1 release, however, the factors that regulate cytokine secretion in the absence of bacterial products are not well defined. P48 is a cytokine recently identified in the supernatant of the human null cell leukemia cell line Reh, which induces differentiation and cytolytic activity in HL-60 cells. P48 has been purified to homogeneity and is distinct from TNF-alpha TNF-beta, IFN-gamma, IL-6, and macrophage CSF. In the present study we examined the ability of P48 to stimulate cytokine release by human peripheral blood monocytes. P48 stimulated the secretion of TNF and IL-1 in a dose-dependent manner. Priming the monocytes with IFN-gamma enhanced P48-induced cytokine release but was not a requirement for secretion. Cytokine secretion was in response to P48 and was not caused by endotoxin contamination. The cytokine-inducing activity of P48 was extremely sensitive to heat treatment but could not be eliminated by using polymyxin B. Polyclonal antisera to P48 completely blocked the cytokine-inducing activity. P48 may be an important new member of the cytokine network involved in the regulation of cytokine secretion by monocytes.
 ...
PMID:P48 induces tumor necrosis factor and IL-1 secretion by human monocytes. 280 97

The IL-2R alpha enhancer contains an 11 bp sequence that resembles kappa B, a regulatory element associated with several genes, including Ig kappa-L chain and human immunodeficiency virus. Although nuclear factor of the kappa-enhancer in B cells (NF-kappa B) binding is activated by PMA, TNF-alpha, and IL-1, activation of the IL-2R alpha enhancer does not consistently correlate with NF-kappa B induction. In this report, we show that TNF-alpha activates NF-kappa B and the human immunodeficiency virus enhancer in the Jurkat T leukemia but does not stimulate the IL-2R alpha enhancer. In contrast, this cytokine, and IL-1, increased IL-2R alpha gene expression in YT-1 cells. Comparing YT-1 and Jurkat T leukemias, we find that the IL-2R kappa B site is required for TNF-alpha and IL-1 stimulation in YT-1 cells, but that plasmids containing this site linked to a heterologous promoter do not respond to these cytokines. These data suggest that upstream regulatory elements in addition to IL-2R kappa B are needed to mediate this cytokine effect. TNF-alpha also synergized with PMA and other cytokines in the stimulation of the IL-2R alpha enhancer in YT-1. Because these effects are not observed in Jurkat cells, the function of the IL-2R kappa B site is cell-specific and likely mediated by different associated transcription factors present in each cell type.
 ...
PMID:Regulation of the IL-2 receptor alpha-gene. Interaction of a kappa B binding protein with cell-specific transcription factors. 280 16

The mechanism of immunodeficiency in adult T-cell leukemia (ATL) patients was studied in vitro. Peripheral blood lymphocytes from ATL patients and ATL cell lines such as Hut 102, MT 1, and MT 2 were not activated to proliferate by the stimulation with concanavalin A and suppressed normal lymphocyte proliferative responses induced with concanavalin A when cultured together. The sera from ATL patients and the culture supernatants from ATL cells and ATL cell lines also suppressed normal lymphocyte proliferative responses induced with concanavalin A. By Sephacryl S-200 column chromatography, the suppressive factors were fractionated as a single peak with the molecular weights of 50,000 to 70,000. The suppressive factors were unstable to acid treatment but stable to the treatment with base, heat, freezing-thawing, and trypsin. The factors suppressed the production of interleukin 2 by T-cells and the responsiveness of T-cells to interleukin 2, but not the expression of interleukin 2 receptors on T-cells and the production of interleukin 1 by monocytes. These results suggest that the immunosuppressive factors produced by ATL cells have some roles in the induction of immunodeficient states in ATL patients.
 ...
PMID:Immunosuppressive factors from adult T-cell leukemia cells. 287 86

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.
 ...
PMID:Interleukin 1 gene expression in adult T cell leukemia. 288 87

The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1 alpha antiserum, but not with anti-IL-1 beta antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1 alpha and that this IL-1 alpha is one of the most important causes of hypercalcemia in ATL patients.
 ...
PMID:Production of bone-resorbing activity corresponding to interleukin-1 alpha by adult T-cell leukemia cells in humans. 289 74

CL 259,763, N-[4-[(4-fluorophenyl)sulfonyl]phenyl] acetamide, is an orally active compound capable of modifying the reactivity of certain lymphoid cell populations affected by the growth of a tumor. The compound augmented the response of lymphocytes from tumor-primed animals to syngeneic tumor cells, resulting in a marked increase in tumor cell destruction. Likewise, it enhanced macrophage inhibitory effects on the growth of tumor cells in vitro. These "activated" macrophages were detectable in peritoneal exudates of treated mice 4 to 12 days after receiving a single oral dose of CL 259,763, with peak activity being demonstrable by day 7. The compound also restored the alloreactivity of lymphocytes from immunodepressed mice bearing the Lieberman plasma cell tumor, possibly by interfering with suppressor cells. Macrophages and lymphocytes from treated mice released significantly more IL-1 and IL-2-like factors in culture than did the control counterparts. Sera from treated mice also possessed more colony stimulating factor than those from normal mice. Immunoadjuvant effects were evident when the compound was administered with an inactivated L1210 leukemia vaccine and it enhanced the effectiveness of cytotoxic chemotherapy when given to mice challenged with P388 murine leukemia. These immunomodulating effects of CL 259,763 may hopefully be exploited in efforts to augment the immune response of the host to a progressively growing tumor.
 ...
PMID:Modulation of the immune response to tumors by a novel synthetic compound, N-[4-[(4-fluorophenyl)sulfonyl]phenyl] acetamide (CL 259,763). 293 49

Blast cell populations from 32 patients with acute non-lymphoblastic leukaemia of various morphological types have been examined for their ability to stimulate allogeneic T lymphocytes from normal donors in one-way mixed leucocyte culture (MLC). At the same time, these leukaemic cell populations were examined for the amounts of major histocompatibility complex Class I and Class II antigens they expressed, and their ability to release interleukin 1 (IL1) in culture both with and without stimulation by lipopolysaccharide. The abilities of the leukaemic cell populations to stimulate in MLC, and to produce IL1, were found to be associated with the expression of morphological characteristics of monocytic differentiation, and correlated significantly. In contrast, no correlation was observed between the extent of Class I or Class II expression and MLC stimulatory ability. Many myeloblast populations of immature phenotype were unable to stimulate allogeneic T cells despite their strong expression of these antigens. This lack of stimulatory ability was not overcome by the addition of exogenous IL1. We therefore conclude that the correlation between the production of IL1 and MLC stimulatory ability does not necessarily imply a cause/effect relationship, and that the interaction between allo-antigen and the T cell receptor together with a supply of lymphokine 'co-stimulator' is not sufficient to activate resting T lymphocytes. The failure of some Class I and II antigen positive leukaemic blasts to stimulate in MLC even in the presence of exogenous IL1 may be due to the lack of other differentiation-associated cell surface molecules necessary for stable cell-cell interaction.
 ...
PMID:Requirements for the stimulation of allogeneic T lymphocytes by acute non-lymphoblastic leukaemia cells. 296 Apr 48

The arborvitae or Thuja occidentale L., one of the Cupressaceae, has rarely been investigated until now. Several authors have demonstrated that allopathic extracts of this plant could be used as strong antiviral agents directed against plant and animal viruses. Polysaccharide fractions with molecular weights ranging between 20,000 and 1,000,000 and higher have been isolated from the aqueous alkaline extract of the herbal parts of T. occidentale L. by ethanol precipitation and fractionation by ultrafiltration. High molecular subfractions of Thujapolysaccharides (TPS) proved to be highly mitogenic on peripheral blood leukocytes. It was demonstrated by the alcalic immune phosphatase-antiphosphatase and Pappenheim staining methods that the mitogenic and cluster-forming activity of TPS cause T cell induction, in particular, of CD 4-positive T-helper/inducer cells as opposed to B cells. The CD-4+ T-helper/inducer cell induction is connected to an increased production of IL-2. The cluster-forming ability and mitogenity of TPS correlates well with the 3H-thymidine uptake and seems to be IL-1 and IFN-gamma dependent as could be shown by blocking the mitogenic effect using anti-IL-1- and anti-IFN antibodies. Whether it is possible to use these polysaccharide fractions as an adjuvant in the therapy of immune deficiency syndromes and cancer must now be further investigated.
Leukemia 1988 Aug
PMID:Mitogenic activity of high molecular polysaccharide fractions isolated from the Cupressaceae Thuja occidentale L. I. Macrophage-dependent induction of CD-4-positive T-helper (Th+) lymphocytes. 297 May 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>