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

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.
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PMID:Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1. 136 53

Tumor necrosis factor (TNF) is a macrophage-derived cytokine that causes hemorrhagic necrosis of several human tumors in vitro. It has a wide range of biologic effects including stimulation of secretion of both granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) by normal adult lung fibroblasts in culture. No in vivo data are available on the effect of exogenously administered TNF on cytokine production. In the studies reported here, we show that G-CSF accumulates in the serum in vivo in response to recombinant TNF (rTNF) administration. At the peak of the response circulating levels of 2-6 ng/ml of biologically active G-CSF are detectable. Surprisingly, circulating levels of GM-CSF, interleukin-3 as well as a number of other cytokines were not detectable within the limits of the assays. The results indicate that the levels of GM-CSF or interleukin-3 are minimally 100-fold lower than the peak levels of G-CSF. These data illustrate the complex interplay that cytokines have in vivo. Understanding these interactions in humans is crucial to the correct use of this new class of agents in the clinic.
Leukemia 1992 Apr
PMID:Recombinant human TNF-alpha stimulates the secretion of granulocyte colony-stimulating factor in vivo. 137 4

Tumor necrosis factor-alpha (TNF) release by monocytes and macrophages may be an important determinant of the physiologic response of the host to neoplastic disease; however, the mechanisms which regulate TNF release by macrophages in hosts with neoplastic diseases are poorly understood. The purpose of this study was to determine if cell membranes and growth medium from human leukemia cell lines and solid tumor cell lines induced TNF release by cultured human blood monocyte-derived macrophages. The capacity for TNF release and direct tumor killing was highest in monocytes cultured for 7 to 11 days. Cell membranes and culture media from K562 erythroleukemia and several small cell lung carcinoma cell lines, including H82, induced the release of up to 1500 TNF units per 10(6) macrophages over 24 hr. By contrast, allogeneic peripheral blood lymphocytes, cell membranes from normal mixed donor peripheral blood leukocytes, or growth medium from normal embryonic lung fibroblasts induced the release of little or no TNF during culture up to 24 hr, suggesting that this macrophage response was specific for tumor cells. Release of TNF by tumor-stimulated macrophages was gradual, peaking 24 hr following the addition of stimuli. Induction of macrophage TNF release was concentration dependent, with half-maximal TNF levels induced by 12.5 and 25 micrograms/ml cell membranes prepared from K562 and H82, respectively. Pretreatment of tumor cell membranes with polymixin B, which inhibits many of the actions of endotoxin, failed to neutralize tumor induction of TNF, suggesting that endotoxin was not responsible for this activity. Depletion of macrophages by treatment with 3C10 monoclonal antibody and complement abrogated tumor-induced TNF release, indicating that macrophages were the source of the secreted TNF. HPLC analysis of H82 growth medium demonstrated a single peak of macrophage activating activity with approximate 40-kDa molecular weight. We have demonstrated that cell membranes and growth medium from some human leukemia and solid tumor cell lines, but not from normal human cells, induce human peripheral blood monocytes and monocyte-derived macrophages to release functionally active TNF. This process may contribute to the host response to some neoplastic diseases.
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PMID:Tumor-stimulated release of tumor necrosis factor-alpha by human monocyte-derived macrophages. 154 64

Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF-alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. 161 21

Tumor necrosis factor (TNF) is a regulatory cytokine that has pleiotropic effects on hematopoietic cell growth and differentiation. The present studies have examined the effects of TNF on the differentiation of phorbol-ester resistant human KG-la leukemia cells. Treatment with 100 U/mL of TNF or 33 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) had no detectable effect on the growth of KG-1a cells. In contrast, TNF, but not TPA, induced cellular aggregation and expression of the ICAM-1 adhesion molecule in KG-1a cells. Furthermore, KG-1a cells responded to TNF, but not to TPA, with a partial down-regulation of c-myc mRNA levels and induction of M-CSF gene transcription. Previous work suggested that TNF induces M-CSF gene expression through activation of phospholipase A2 and eicosanoid production. The present studies also demonstrate that TNF stimulated phospholipase A2 activity. In contrast, there was no detectable increase in phospholipase A2 activity following TPA treatment. These results indicate that: 1) certain characteristics of the differentiated monocytic phenotype were induced by TNF in the phorbol ester-resistant KG-1a line, and 2) treatment with TNF and not TPA was associated with activation of phospholipase A2 during induction of monocytic differentiation in these cells.
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PMID:Induction of monocytic differentiation by tumor necrosis factor in phorbol ester-resistant KG-1a cells. 169 25

We have previously demonstrated (Guan X.-P., Hromchak, R. A., and Bloch, A. (1989) Cancer Commun. 1, 111-115) that ML-1 human myeloblastic leukemia cells differentiate to monocyte/macrophage-like cells by the sequential action of competence and progression factors. Tumor necrosis factor-alpha, transforming growth factor-beta, and the phorbol ester tetradecanoylphorbol acetate were found to induce competence, whereas a 77-kDa glycoprotein (DF77) isolated from mitogen-stimulated human leukocyte-conditioned medium initiated progression. In this communication we show DF77 to be an isoform of human transferrin. Hemin or soluble iron complexes did not induce differentiation progression, suggesting that the participation of transferrin in ML-1 cell differentiation may not be related to its iron-carrying capacity.
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PMID:Identification of transferrin as a progression factor for ML-1 human myeloblastic leukemia cell differentiation. 186 25

Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host; They are cytokines, monoclonal antibodies, and immunomodulating agents produced by effector cells which are called macrophage, NK cells and lymphocytes of cancer patients. Recent genetic engineering enables mass production of these substances, and their clinical application in treating human cancers is expected to take place in the near future. In this paper, the recent trend of cancer treatment, using various cytokines are briefly introduced, namely interferon, interleukin-2, tumor necrosis factor and colony stimulating factor. Although IL-2 is effective for the activation of T-lymphocyte, intravenous injection of IL-2 is not so effective for treatment of cancer-patients. On the other hand, IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. The clinical study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration. Tumor necrosis factor, a cytotoxin derived from macrophages shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Clinical study was performed on leukemia patients who showed marked decreases of percentage of leukemic cells in peripheral blood. Moreover, local injection of TNF was very effective for the decrease of tumor size in patients with hepatoma and subcutaneous tumor. In addition, to clinical results using CSF and interferon are reported.
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PMID:[Recent trends in cancer treatment using cytokines]. 247 55

Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived cytokine elicited during cellular responses to various microbial infections. TNF-alpha exerts direct cytotoxicity toward some tumor cells in vitro and produces hemorrhagic tumor necrosis in vivo. In human promyelocytic HL-60 leukemia cells, human recombinant TNF-alpha (rTNF-alpha) exhibits a small early proliferative effect (within 48 h), followed by marked cytostatic activity at 96 h after the addition of rTNF-alpha. Cytostasis is contiguous with an induction of cell differentiation along the monocyte/macrophage lineage. The cell proliferation effects and the induction of the differentiated phenotype are preceded by an approximate 5-fold increase in c-fos mRNA levels within 90 min after rTNF-alpha treatment of log phase HL-60 cells. Nuclear in vitro transcription assays indicate that the effect of rTNF-alpha on c-fos mRNA abundance is controlled at the transcriptional level. We have also used a postembedding immunocolloidal gold electron microscopy technique to localize and semiquantitate pp55c-fos proto-oncoprotein levels in the nucleus of both control and rTNF-alpha-treated HL-60 leukemia cells. In response to rTNF-alpha, we have observed a rapid and transient accumulation of pp55c-fos in discrete nuclear substructures within 2 h after treatment. C-fos staining appears in clusters, which are preferentially localized over semi-condensed chromatin and interchromatin granules. These results suggest that pp55c-fos is involved in the signal transduction system initiated by rTNF-alpha during the induction of HL-60 differentiation.
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PMID:Induction of macrophage-like differentiation of HL-60 leukemia cells by tumor necrosis factor-alpha: potential role of fos expression. 249 5

Tumor necrosis factor-alpha and transforming growth factor-beta, like 12-O-tetradecanoylphorbol 13-acetate, induce differentiation of ML-1 human myeloblastic leukemia cells along the monocyte path. As measured at 5 min following exposure of the cells to either of these agents, extensive translocation of protein kinase C from the cytosolic to the membrane fraction occurred. A correlation was observed to exist between protein kinase C translocation, cell differentiation, and cessation of cell growth induced by transforming growth factor-beta and tumor necrosis factor-alpha.
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PMID:Induction of protein kinase C translocation and cell differentiation in ML-1 human myeloblastic leukemic cells by tumor necrosis factor-alpha, transforming growth factor-beta, or tetradecanoylphorbol acetate. 263 23

Tumor necrosis factor (TNF) is a Mr 17,000 cytokine produced by macrophages. We have recently demonstrated that TNF is also produced by transformed human epithelial cells. The present studies have examined TNF expression in human myeloid leukemic cells. We have monitored TNF expression at a cellular level using alkaline phosphatase detection of a biotinylated TNF cDNA probe in situ. Using this approach, TNF transcripts were detectable in HL-60 cells induced along the monocytic lineage by phorbol ester but not in uninduced cells. The specific detection of TNF RNA at a cellular level was supported by the absence of histochemical staining in RNase-treated cells and when using biotinylated pBR322 plasmid without insert. These studies were extended to preparations of purified acute myeloblastic leukemia cells. The results demonstrate that TNF is expressed in myeloblasts in eight of nine patients with AML. In each preparation of myeloblasts with detectable TNF RNA, transcripts were present at 89-98% of the cells. The identification of TNF RNA in situ was also associated with the detection of TNF protein in leukemic blasts by indirect immunofluorescence. Moreover, the detection of TNF protein in these preparations of myeloblasts was confirmed by immunoblotting. However, using this approach to examine AML cells before and after purification indicated that TNF expression is induced as a result of the enrichment procedures. Thus, certain populations of purified myeloid leukemic cells are capable of expressing TNF at both the RNA and protein levels.
Leukemia 1989 Jan
PMID:Detection of tumor necrosis factor gene expression at a cellular level in human acute myeloid leukemias. 264 77


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