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)

TCR gamma delta expressing T cell clones are able to exhibit in vitro strong cytolytic activity against cultured tumor cell lines as the myeloid K562 or the Burkitt's lymphoma Daudi cell line. We investigate the possibility of developing TCR gamma delta bearing T cell lines from peripheral blood of 2 leukemic patients in complete remission in order to study their ability to kill autologous leukemic cells. T lymphocyte clones are obtained by limiting dilution of lymphocytes from the blood of patients with an acute lymphoblastic leukemia (ALL). The T cell clones are first selected for their CD8- CD4-phenotype and then for their ability to react with the monoclonal antibody anti-CD3 without presenting reactivity with a monoclonal antibody directed against the TCR alpha beta. Further biochemical studies have indicated that the CD3 associated structure expressed on the cell membrane of these T cell clones is a gamma delta heterodimer. Functional analysis have indicated that these cloned cells are able to kill in a classical cell mediated lysis assay the autologous leukemic cells only when also LAK activity is observed. Thanks to this clonal expansion 10(10) cells/week indefinitely only 1 sample of peripheral blood will be necessary. Would these results be found with other leukemic patients, we propose to use this procedure for a possible application of killer cells for maintenance therapy of leukemia.
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PMID:Human CD3 gamma delta + activated lymphocytes exhibit killer activity in vitro against autologous leukemic cells. 252 19

The Hodgkin-associated Ki-1 antigen occurs in two different molecular forms. The 120-kDa membrane-associated form is a phosphorylated glycoprotein, which is derived from a non-phosphorylated intracellular 84-kDa apoprotein that is co-translationally N-glycosylated with a carbohydrate portion of 6 kDa. The other form of the Ki-1 antigen is a non-glycosylated phosphoprotein of 57 kDa which only occurs intracellularly. Both forms of the antigen are phosphorylated at serine residues. Enzymatic cleavage with sialidase reduced the 120-kDa membrane antigen by about 15 kDa, while its 90-kDa precursor and the 57-kDa intracellular form of the Ki-1 antigen remained unaltered. Pulse-chase experiments revealed that the 57-kDa and 90/120-kDa molecules are synthesized independently of each other. Four to eight hours after synthesis, the degradation of the 120-kDa molecule to a 105-kDa membrane-associated intermediate begins. This is further processed and appears in the cell supernate as a 90-kDa molecule. Hodgkin's disease-derived, Epstein-Barr virus-transformed cell lines and the acute T cell leukemia line MOLT-4 contain both forms of the Ki-1 antigen, whereas only the 57-kDa intracellular antigen is expressed in U266/B1 myeloma cells, in the Burkitt lymphoma cell lines Raji and Daudi and in acute promyelocytic HL-60 leukemia cells.
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PMID:The Hodgkin-associated Ki-1 antigen exists in an intracellular and a membrane-bound form. 254 29

Clinical and experimental data suggest a role for the immune response in preventing leukemic relapses following allogeneic bone marrow transplantation the graft-versus-leukemia (GVL) effect. In the context of an allogeneic BMT, a number of different immune mechanisms mediated by donor cells may be responsible for the GVL effect. We have approached this question by using limiting dilution cultures of alloactivated human lymphocytes to analyze the in vitro allogeneic cytolytic response against fresh allogeneic leukemia. Initial results in the limiting dilution assays with split culture analyses demonstrated frequent alloreactive cytolytic T lymphocyte precursors that destroyed remission peripheral blood lymphocytes and leukemic cells from the allogeneic leukemic patient. These assays also demonstrated frequent lymphokine-activated killer (LAK) cell precursors that lysed both the LAK sensitive Daudi line and the allogeneic leukemia. In these experiments, isolated cultures also showed cytolytic activity directed against the allogeneic leukemic blasts without activity against remission PBL, or the LAK-sensitive Daudi cell line. Two T cell lines (ABL1 and ABL2) isolated from an LDA, demonstrated this form of specificity, mediating destruction specifically against the allogeneic acute lymphoblastic leukemic cells. Both cell lines ABL1 and ABL2 were CD3+, TCR alpha beta +, and CD4+. These 2 cell lines mediated little or no cytotoxicity against a large panel of other targets tested (natural killer sensitive and resistant cell lines, allogeneic PBL, and allogeneic fresh leukemic blasts). Antibody-blocking experiments revealed a role for the CD3-TCR receptor of both cell lines in lysis of leukemic cells; the CD4 and MHC class II molecules were clearly involved in the lysis by the ABL1 cell line. Specificity of recognition for the allogeneic leukemic blasts was further confirmed by unlabeled target competitive inhibition studies. The mechanism of the preferential lysis of leukemia by the alloactivated T cell lines described in this paper remains uncertain. Nevertheless, these leukemic-specific populations provide a means by which the human GVL effect may be further studied in vitro.
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PMID:Specific recognition of human leukemic cells by allogeneic T cell lines. 257 Dec 6

The present investigation demonstrates that leukoregulin, a cytokine secreted by natural killer (NK) lymphocytes up-regulates the sensitivity of tumor cells to lymphokine-activated killer (LAK) cell cytotoxicity. It has been previously established that leukoregulin increases the sensitivity of sarcoma, carcinoma and leukemia cells to natural killer (NK) cell cytotoxicity. Tumor cells were treated with leukoregulin for 1 h at 37 degrees C and tested for sensitivity to NK and LAK cytotoxicity in a 4-h chromium-release assay. NK-resistant Daudi, QGU and C4-1 human cervical carcinoma cells became sensitive to NK cytotoxicity after leukoregulin treatment, and their sensitivity to LAK was increased two- to sixfold. Y-79 retinoblastoma cells, which are moderately sensitive to NK and very sensitive to LAK, became increasingly sensitive (two- to four-fold) to both NK and LAK cell cytotoxicity. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant interleukin-1 (alpha and beta), recombinant interferon gamma, recombinant tumor necrosis factor or combinations of the latter two failed to up-regulate tumor cell sensitivity to NK and LAK cell cytotoxicity. However, treatment with recombinant interferon gamma for 16-18 h, GM-CSF and interleukin-1 beta for 1 h induced a state of target cell resistance to both NK and LAK cell cytotoxicity. Leukoregulin may have an important physiological function in modulating NK and LAK cell cytotoxicity by increasing the sensitivity of target cells to these natural cellular immunocytotoxicity mechanisms.
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PMID:Leukoregulin up-regulation of tumor cell sensitivity to natural killer and lymphokine-activated killer cell cytotoxicity. 268 71

In the current study, we investigated the cytotoxic ability of peripheral blood mononuclear cells (PBMC) recovered from patients with acute nonlymphoblastic leukemia (ANLL) in complete remission (CR) against natural killer (NK)-sensitive, NK-resistant, autologous and allogeneic leukemic target cells taken at diagnosis. Our purpose was to define the role played by cytotoxic mechanisms in the control of leukemic cell growth in ANLL. Experiments were carried out at resting conditions and after in vitro activation with recombinant interleukin-2 (rIL-2) and anti-CD3 monoclonal antibody (moAb). At resting conditions, PBMC recovered from ANLL patients displayed a NK function that was not significantly different from controls (mean +/- standard error of the mean [SEM]: 21.9% +/- 3.9% versus control values of 27.5% +/- 2.9%; the P value was not significant [NS]), but they were unable to show cytotoxic activity against autologous and allogeneic leukemic cells. After in vitro boosting with rIL-2, PBMC were able to generate lymphokine activated killer (LAK) cells, as demonstrated by an increased killing of NK-resistant Daudi targets (16.3% +/- 2.7%). Although LAK activity was quantitatively lower than in control subjects (mean +/- SEM: 16.3% +/- 2.7% versus control values of 79.8% +/- 3.1%; P less than 0.001), it still exerted a cytotoxic effect against autologous and allogeneic leukemic cells. Similar results were obtained when anti-CD3 moAb was used as a stimulus in vitro. Our data suggest that nonspecific cytotoxic cells may be triggered to exert an in vitro cytotoxic effect on leukemic cells, which could possibly play a key role in vivo in the control of leukemic cell growth regulation.
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PMID:Functional analysis of cytotoxic cells in patients with acute nonlymphoblastic leukemia in complete remission. 278 99

Signals from many receptor-ligand interactions are mediated by enhancement of phospholipid hydrolysis which generates metabolic intermediates stimulating protein kinase C (PKC) and elevating cellular calcium. Pharmacologic agents such as phorbol 12, 13-dibutyrate (PDBu) and ionomycin selectively stimulate PKC and elevate intracellular calcium to directly stimulate downstream mechanisms critical to cell growth and function. This study examines the effects of PDBu, ionomycin, and rIL-2 on childhood ALL blasts of early B lineage with respect to various aspects of cell activation, including DNA synthesis, induction of non-MHC restricted tumoricidal activity, and changes in morphology and phenotype. Five childhood ALL samples were tested. A marked heterogeneity was seen among the ALL samples with respect to in vitro growth following manipulation with PDBu, ionomycin, and/or rIL-2, whereas normal peripheral blood lymphocytes (PBL) were consistently stimulated to grow with the combination of PDBu and ionomycin. Growth responsiveness did not appear to correlate with morphologic or phenotypic classification of the leukemia samples. Four of the five leukemia samples developed substantial non-MHC restricted cytotoxicity to K562 (natural killer cell (NK) sensitive) and Daudi (NK resistant) targets in response to rIL-2. This functional cytotoxic response correlated with morphologic changes in the cells and the appearance of granules. Phenotypic analyses of the ALL samples at the time of their peak cytotoxic function were consistent with the fresh ALL phenotype and showed no major change in cell populations. Three of the five ALL samples also retained rIL-2 induced cytotoxic capabilities when exposed simultaneously to the combination of PDBu and ionomycin, whereas rIL-2 induced tumoricidal activity in normal PBL and bone marrow cultures was inhibited by these reagents. These data show that morphologically and phenotypically similar ALL blasts have heterogeneous proliferative responses to the PKC and calcium modulators PDBu and ionomycin, as well as to rIL-2. Cytotoxic responses are also different from those of normal PBL and bone marrow cells with respect to kinetics and responsiveness to inducing agents. Thus current morphologic and phenotypic classifications of ALL may not adequately reflect the heterogeneity of this disorder as described here.
Leukemia 1989 Aug
PMID:Induction of tumoricidal activity and alterations of growth by interleukin-2 and manipulation of protein kinase C and cytosolic calcium in childhood acute lymphocytic leukemia cells. 278 55

The effects of 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] on proliferation and de novo DNA synthesis were studied in the following established human leukemia cell lines: lymphoblastic T-cell lines HPB-ALL, CCRF-HSB-2, p12/lchikawa, and HPB-MLT; adult T-cell leukemia- (ATL) and human lymphotropic virus type I (HTLV-I)-infected T-cell lines HUT102, HUT-102B2, MT-1, MT-2, MJ, C2/MJ, KH-2, KH-2Lo, HPB-CTL-1, and ATN-C1; ATL-derived B-cell lines ATL-BK9 and ATL-BK10; lymphoblastic B-cell line Daudi; and myelocytic-monocytic lineage cell lines HL-60 and U937. 1,25(OH)2D3 inhibited proliferation and de novo DNA synthesis of phytohemagglutinin-P-activated T-cells and certain established HTLV-I-positive T-cells. However, it did not inhibit immature lymphoblastic T- and B-cells or ATL-derived B-cells. The degree of inhibition depended on the dose of 1,25(OH)2D3 and the heterogeneity of the established HTLV-I-positive T-cells. KH-2 and subclone KH-2Lo were markedly inhibited, and HPB-CTL-1 was moderately inhibited. Marked inhibition of DNA synthesis in KH-2Lo cells was observed in the proliferative phase of the cell cycle. No inhibition of KH-2Lo proliferation or expression of interleukin-2 and transferrin receptor was noted after removal of 1,25(OH)2D3 from the culture medium. 1,25(OH)2D3 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced multinucleated cell formation of various HTLV-I-positive T-cell lines and TPA-induced HTLV-I p19 expression in KH-2Lo cells.
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PMID:Effect of 1 alpha,25-dihydroxyvitamin D3 on proliferation of activated T-cells and established human lymphotropic virus type I-positive T-cell lines. 288 43

In this report we describe the production and characterization of a monoclonal antibody to the human promyelocytic leukemia cell line HL-60. The antibody, NC-2, is of the IgG1 subclass and precipitates a 50-Kd protein from 125I-labeled HL-60 cells. The antigen is insensitive to treatment with trypsin, papain, or neuraminidase. NC-2 did not react with a number of established human cell lines, including Daudi, Molt-4, K562, U937, KG-1, CEM, Raji, and Gash-P. Neutrophils and monocytelike cells derived from HL-60 cells that were induced to differentiate continued to express the antigen. NC-2 reacted with all peripheral-blood cells except erythrocytes from eight (5%) of 150 normal individuals tested. Bone marrow samples from patients with myelogenous leukemias were more frequently reactive with NC-2 than were those from normal individuals (12/33 v 1/10). Family studies indicated that the antigen was inherited in an autosomal-dominant manner. These findings suggest that the expression of the above alloantigen is associated with an increased incidence of leukemia.
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PMID:Identification of a leukocyte alloantigen with a high-frequency expression in leukemia patients. 291 90

Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin's lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray-irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested. These results may have therapeutic relevance in patients undergoing interferon treatment who require bone marrow transplantation, as the complete elimination of tumor cells by marrow-purging procedures may be hampered by this increased survival in the presence of interferon.
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PMID:Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging. 292 Feb 7

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) was used to examine the phenotypic changes in three African Burkitt's lymphoma cell lines, P3HR1, Daudi, and Raji. Cells were cultured with a nanogram concentration of TPA for up to seven days and then analyzed by flow cytometry and an immunoperoxidase staining method. The cells were stained with a panel of monoclonal antibodies reactive with B lymphocytes or B cell leukemia/lymphomas, and an antibody to the enzyme terminal deoxynucleotidyl transferase (Tdt). All three cell lines were found to express more HLA-linked DC/DS (Leu 10) antigen, while demonstrating a concomitant decrease in the expression of common acute lymphoblastic leukemia antigen (CALLA) and terminal deoxynucleotidyl transferase after TPA induction. The other antigens including Ig, BA1, BA2, Tac, Leu 8, Leu 1, C3bR, Leu 12, and Leu M5 showed no significant changes. The marker expression and differentiation pattern of these African Burkitt's lymphoma lines are very similar to those of pre-B cells except for the surface IgM expression observed in Daudi cells. The expression of CALLA and Tdt in African Burkitt's lymphoma is probably not the result of an Epstein-Barr virus infection, but may in fact reflect the true nature or origin of tumor cells. We conclude that African Burkitt's lymphoma cells are derived from an early stage of B-cell differentiation closely related to, but more mature than pre-B cells.
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PMID:Induction of differentiation of African Burkitt's lymphoma cells by phorbol ester: possible relation with early B cells. 295 57


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