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)

Rat basophilic leukemia (RBL-2H3) cells undergo morphological and cytoskeletal changes during antigen-induced secretion of allergic mediators. The exact role these changes play in the process of secretion is unclear. Using confocal microscopy we now show that PMA+A23187 causes extensive F-actin rearrangements during secretion of [3H] 5-HT. We also describe for the first time the association of myosin with F-actin during this secretory process. In unstimulated cells, myosin and F-actin are concentrated at the plasma membrane with no evidence of stress fibres. Upon addition of PMA or A23187, both F-actin and myosin are rearranged into membrane ruffles and discrete aggregations (foci), followed by the formation of parallel stress fibres located on the ventral membrane. This is in contrast to reports in other cell types in which PMA has been described as causing the disruption of F-actin stress fibres. The time course of secretion coincides with the formation of the foci and ruffles whilst the stress fibres form after the majority of secretion has occurred. These changes are accompanied by a 40% decrease in cell height and a two-fold increase in cell spreading and they occur in the absence of extracellular calcium but are inhibited by the protein kinase C inhibitor, Bisindolylmaleimide, which also inhibits secretion. The formation of myosin-decorated stress fibres, foci, and ruffles is not sufficient to cause secretion, as PMA alone induces these changes without any secretion. The relevance of actin and myosin rearrangements for the regulation of secretion is discussed.
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PMID:PMA and calcium ionophore induce myosin and F-actin rearrangement during histamine secretion from RBL-2H3 cells. 753 11

L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.
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PMID:Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax. 757 5

The two tumor necrosis factor receptors (TNF-Rs) exist in their soluble form in different biological fluids. In this study we investigated the concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) in the culture supernatants of leukemic cells and in the serum obtained from 33 patients: 12 with hairy cell leukemia (HCL) and 21 with B cell chronic lymphocytic leukemia (B-CLL). In seven patients with HCL, sTNF-Rs were also evaluated following in vivo treatment with interferon-alpha (IFN-alpha). Purified leukemic cells from patients with HCL and B-CLL spontaneously released sTNF-R75 but not sTNF-R55. The levels of sTNF-R75 were higher in supernatants obtained from cultured hairy cells than from cultures of B-CLL cells. The shedding of sTNF-R75 was further increased both in HCL and B-CLL subjects by some B cell-related stimuli, including BCGF, PMA, SAC and was partially inhibited by IFN-alpha in patients with HCL. Sera from HCL patients presented increased levels of both sTNF-Rs with respect to normal controls. Treatment of HCL patients with IFN-alpha resulted in a decrease in serum levels of sTNF-Rs, particularly sTNF-R75. These findings suggest that leukemic cells account for the increased serum levels of sTNF-R75 observed in patients with HCL and B-CLL, but not for sTNF-R55.
Leukemia 1995 Jun
PMID:Leukemic cells in hairy cell leukemia and B cell chronic lymphocytic leukemia release soluble TNF receptors. 759 68

A new pre-B cell leukemia cell line, NALM-26, was established from the peripheral blood of a 24-year-old male patient with acute pre-B cell leukemia. NALM-26 is unique in its expression of T cell-associated CD5 and myeloid cell-associated CD13 antigens. Interleukin-7 (IL-7) receptor (CDw127) was detected by flow cytometric analysis. After PMA treatment, NALM-26 was induced to express CD20, CD25 and CD28, and to increase its expression of both CD5 and CD13. The expression of CDw127 was down-modulated.
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PMID:Establishment and characterization of new pre-B cell leukemia cell line NALM-26. 759 11

Lipocortin 1, a putative mediator of the anti-inflammatory actions of glucocorticoids, is present intracellularly in a variety of tissues including human peripheral blood leukocytes. We investigated the presence of lipocortin 1 in human leukocyte subsets using permeabilization flow cytometry. Constitutive lipocortin 1 was detected in U937 myelomonocytic leukemia cells, and lipocortin 1 was increased by treatment with PMA or PMA+IFN-gamma (P < 0.05) but not by dexamethasone. Lipocortin 1 was present in all leukocyte subsets except B lymphocytes (CD19/20+, P < 0.001). Lipocortin 1 content was maximal in monocytes and polymorphonuclear neutrophils and least in lymphocytes (P < 0.001). Monocyte lipocortin 1 was strongly associated with surface expression of CD14 and HLA-DR. Among non-B lymphocytes, a range of lipocortin 1 fluorescence was observed. Lipocortin 1 fluorescence was greatest in natural killer cells (CD56+, P < 0.001) and CD57+ cells, but T cell subset markers did not otherwise discriminate variations in lipocortin 1. Induction of lymphocyte proliferation by PHA, anti-CD3, Con A, superantigen, and SAC was not associated with significant shifts in lipocortin 1 content. Dexamethasone (10(-10)-10(-6) M) did not induce increases in PB leukocyte lipocortin 1. We conclude that lipocortin 1 content in human leukocytes varies significantly among phenotypic subsets. This has significance for the investigation of inflammatory disease where certain cell types predominate.
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PMID:Detection of intracellular lipocortin 1 in human leukocyte subsets. 761 38

The exact mechanism of immunosuppression by thalidomide is poorly understood. A common denominator in the pathogenesis of graft-vs.-host disease, graft rejection, reactional lepromatous leprosy, and autoimmune disorders modulated by thalidomide is the activation of T lymphocytes culminating in the synthesis of interleukin-2 (IL-2), the expression of high-affinity IL-2 receptors, and the induction of proliferation. We investigated the effect of thalidomide on the production of IL-2 by the human leukemia cell line Jurkat through induction of IL-2 gene enhancer activity and through the presence of IL-2 in supernatants. beta-galactosidase activity, encoded by a reporter lac z construct and controlled by a transcription factor in thalidomide-treated PMA- and ionomycin-stimulated Jurkat cells, was similar (97 +/- 1.33%; p > 0.1) to non-thalidomide-treated controls at all drug concentrations tested. IL-2 enhancer-driven beta-galactose activity of thalidomide-treated and stimulated cells was also similar to that of untreated controls (p > 0.2). The IL-2 production of activated nontransfected Jurkat cells was gauged by using the IL-2-dependent cell line HT-2 as a readout and by ELISA. Jurkat cells were subcloned by limiting dilution. Bulk cultures and three subclones (J.5.2.5., J.5.2.9., and J.5.3.8.) were assayed at 6, 12, and 24 hours after PHA/PMA-induced stimulation. No inhibitory effect on the IL-2 production by thalidomide could be detected at any of the drug concentrations tested (5-30 micrograms/mL), whereas 10 to 100 ng/mL of cyclosporine inhibited the IL-2 production by 95 to 100%. In addition, we observed neither inhibition of IL-2-dependent proliferation of HT-2 nor inhibition of PHA-induced proliferation of peripheral mononuclear cells by thalidomide at all drug concentrations used (5-30 micrograms/mL). These results do not support the possibility of a modulatory effect on the immune response by thalidomide via IL-2 production and IL-2 response.
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PMID:Does thalidomide affect IL-2 response and production? 763 84

We have isolated a subclone (JCS) of the WEHI 3B myelomonocytic leukemia, which acquires the characteristics of mature macrophage lineage cells in the presence of PMA or noncytotoxic concentrations of TNF-alpha (600-1200 U/ml). JCS cells were compared with D+ and D- subclones of WEHI 3B. Unlike D+ cells, JCS cells did not produce differentiated granulocyte-macrophage colonies in the presence of postendotoxin serum or recombinant G-CSF. Stimulation with PMA or TNF-alpha reduced proliferation of JCS cells. TNF-alpha decreased the level of cell surface J11D antigen with concurrent increased expression of Mac-1 and FcR antigens and phagocytic activity. These TNF-alpha-mediated effects were enhanced by addition of IFN-gamma to the cultures. Furthermore, differentiation-inducing activity of PMA could be prevented using neutralizing anti-TNF-alpha antibodies. The results indicate that exogenous TNF-alpha can act as a differentiative agent for JCS cells and that endogenous TNF-alpha is the active substance when PMA is used to stimulate macrophage differentiation of JCS cells.
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PMID:Monocytic differentiation of a myelomonocytic leukemic cell (WEHI 3B JCS) is induced by tumour necrosis factor-alpha (TNF-alpha). 768 66

Interleukin-3 (IL-3), a cytokine known to be produced by activated T lymphocytes, mast cells, eosinophils and neutrophils, is a potent stimulator of normal haemopoiesis, particularly megakaryocytopoiesis. However, it remains unknown whether leukaemic megakaryoblasts can produce IL-3 and whether IL-3 is involved in the pathological process of megakaryoblastic leukaemia. In this study, several human leukaemia cell lines with or without megakaryocytic features, the DAMI, MEG-01, HEL, K562, HL-60 and U937, were chosen as the models. It was first demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay that IL-3 was expressed in DAMI and MEG-01 cells, but not in other cell lines, although two erythroleukaemic cells, the HEL and K562, also possess some megakaryocytic features. Interestingly, the mRNA for IL-3 receptor was detected in nearly all the cell lines except K562 cells, suggesting that expression of IL-3 and its receptor may be dissociated in most of the cell lines and that co-expression of IL-3 and its receptor exists in megakaryoblastic cell lines, the DAMI and MEG-01. Of the cell lines which did not express IL-3 under unstimulated condition, only HEL cells were able to express IL-3 mRNA after treatment with PMA for 72 h. Furthermore, the proliferation of DAMI and MEG-01 cells could be enhanced in the presence of IL-3 and suppressed by the anti-IL-3 antibody and the IL-3 antisense oligodexyonucleotides (ODNs). These findings indicate that IL-3, as an autocrine growth factor, is involved in the growth of some megakaryocytic leukaemia cell lines.
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PMID:Interleukin-3 is an autocrine growth factor of human megakaryoblasts, the DAMI and MEG-01 cells. 781 61

Lysozyme was purified from exocytosed granule material from PMA-stimulated human neutrophils by polyethyleneglycol precipitation, cation exchange chromatography and molecular sieve chromatography. Rabbit antibodies were biotinylated and affinity purified on a lysozyme column, for subsequent development of a novel ELISA. This ELISA for lysozyme is sensitive and accurate, and applicable to determination of lysozyme in neutrophils and plasma.
Leukemia 1995 Jan
PMID:Purification of lysozyme from human neutrophils, and development of an ELISA for quantification in cells and plasma. 784 19

Morphologically HL-60 leukaemia cells largely resemble promyelocytes and can be induced to terminally differentiate in vitro. Upon reaching terminal maturation these cells rapidly undergo apoptosis. Using three chemotherapeutic agents with known apoptosis inducing capability, the susceptibility of RA - and PMA - differentiated cultures was monitored by morphological means and flow cytometry. We observed that as cells with morphological characteristics of mature granulocytes/monocytes became more prominent in the populations, there was an increased resistance to apoptosis. The inhibition of the typical internucleosomal DNA fragmentation was confirmed by agarose gel electrophoresis. However, activation of a CA+/Mg+ independent endonuclease in isolated nuclei was not affected. Flow immunocytometry revealed reduced levels of c-myc and bcl-2 oncoproteins in RA and PMA treated cells. These observations suggest that HL-60 derived granulocytes/monocytes become increasingly resistant to the induction of apoptosis and that this resistance is independent of c-myc and bcl-2 expression. Together these results demonstrate that the phenotypic changes associated with RA and PMA induced differentiation, inhibit a critical step in the progression of apoptosis.
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PMID:Increased resistance to apoptosis associated with HL-60 myeloid differentiation status. 784 52


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