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)

A human promyelocytic leukaemia cell line, HL-60 cells, did not show accessory cell (AC) function to potentiate the proliferation of human T cells induced by anti-CD3 antibody coupled to latex beads (alpha T3-L). This was found to be at least due to the inability of HL-60 cells to express certain molecules which are inducible with interferon-gamma (IFN-gamma) on mature monocytes and are necessary for interaction with T cells. HL-60 cells acquired the ability to express such surface molecules by stimulation with IFN-gamma when the cells were pretreated with 1,25-dihydroxyvitamin D3 (Vit D). The effect of Vit D was reversible, that is, the AC function of the HL-60 cells was lost when the cells were cultured in Vit D-free medium for 7 days. It was also found that HL-60 cells treated with IFN-gamma and then with Vit D did not show significant AC function. The flow cytometric analysis showed that the expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) was highly increased on HL-60 cells when stimulated with IFN-gamma after treatment with Vit D. The expression of ICAM-1 was also induced with IFN-gamma on untreated cells but in lower amounts. Monoclonal antibodies against ICAM-1 and HLA-DR inhibited the alpha T3-L-induced T-cell proliferation, indicating that these molecules are at least required for contact-mediated AC function. Thus our study revealed that HL-60 cells express cell surface interaction molecules necessary for potentiating the T-cell proliferation through two steps, differentiation with Vit D to mature monocyte-like cells followed by stimulation with IFN-gamma.
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PMID:Development of the cell contact-mediated accessory function for T-cell proliferation in a human promyelocytic leukaemia cell line, HL-60, by 1,25-dihydroxyvitamin D3. 135 May 68

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

The expression and function of neural cell adhesion molecule (NCAM, CD56, Leu19) on leukaemic blasts was investigated. The expression of NCAM was frequent (64%) in 14 studied cases of acute myeloid leukaemia (AML) but not in chronic lymphocytic leukaemia (CLL: 1/3 cases positive) or immunocytoma (IC: no positivity). No correlation with the expression of other AM (intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1). VLA beta chain) or with AML type, according to FAB classification, was observed. Blocking of NCAM with anti-Leu 19 MoAb on AML targets resulted in a significant decrease of their susceptibility to LAK killing and in inhibition of conjugate formation. In the case of B prolymphocytic leukaemia (B-PLL) which did not express ICAM-1 or LFA-1 but was NCAM+, a complete resistance to LAK activity and lack of conjugate formation was observed. Blocking of NCAM on LAK effectors did not decrease their cytotoxic activity. Our results suggest that NCAM, in the presence of other AM, may have a supportive role in adhesion of leukaemic targets to LAK effectors.
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PMID:A supportive role of neural cell adhesion molecule (NCAM) in adhesion between leukaemic blasts and cytotoxic lymphocytes. 137

Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion receptors which are involved include CD44 and the integrin family, CD11/CD18. In this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for the expression of these adhesion molecules, and for the way in which cytokines are able to modulate the levels of these receptors. B-CLL cells express significant but variable levels of LAM-1 and high levels of CD44. In contrast, these cells exhibit very low or absent amounts of surface CD11a, CD11b, or CD11c. Most CLL cells expressed no detectable levels of intercellular adhesion molecule-1 but some cases show levels of up to 30%. Following 24 h incubation with interferon alpha (500 U/ml), surface LAM-1 expression on peripheral blood E-negative cells from CLL patients rose to 330 +/- 127% of levels on control cells incubated with medium alone (n = 13, p less than 0.0005). Interleukin 4 (1 ng/ml) and interferon gamma (100 U/ml) also increased surface LAM-1 levels on these cells to 218 +/- 119% (n = 8, p less than 0.001) and 245 +/- 116% (n = 5, p less than 0.001) of control levels respectively. Induction of LAM-1 expression occurred over 48 h (greater than 50% of the increase was seen in the first 24 h) in a dose-dependent manner and required protein synthesis. The induction of LAM-1 expression on the malignant cells may, by altering the homing behaviour of these cells, relate to the reduction in peripheral leukaemic cells seen following treatment with interferon alpha in CLL.
Leukemia 1992 May
PMID:Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on chronic lymphocytic leukaemia cells. 137 97

NK cells and certain CTL can recognize and lyse targets without restriction by the MHC. NK cells do not express CD3/TCR complexes and the membrane receptors participating in MHC-unrestricted cytotoxicity are largely unknown. We demonstrate that YT2C2, a human NK leukemia cell line, expresses the CD28 differentiation Ag and can spontaneously lyse both murine and human cell lines expressing B7, a B cell- activation Ag that is a ligand for CD28. The participation of CD28/B7 interactions in MHC-unrestricted cytotoxicity mediated by YT2C2 cells was demonstrated by correlation of target sensitivity with levels of B7 expression, inhibition of cytotoxicity by anti-CD28 or anti-B7 mAb, and by making both murine and human cell lines susceptible to YT2C2-mediated lysis by genetic transfection with expression vectors containing B7 cDNA. However, CD28/B7 interactions alone were insufficient to initiate cytotoxicity. mAb inhibition experiments and selection of CD54- (intercellular adhesion molecule-1) deficient B cell targets indicated that CD11a/18 (lymphocyte function-associated Ag-1) also cooperated in CD28/B7-dependent cytotoxicity. The requirement for both CD28/B7 and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 interactions in YT2C2-mediated MHC-unrestricted cytotoxicity was confirmed by demonstrating that efficient lysis of murine L cells required cotransfection with both B7 and intercellular adhesion molecule-1. These findings support the concept that MHC-unrestricted cytotoxicity may not be due to a unique receptor, but may result from interactions between an appropriate array of "adhesion" molecules with their ligands.
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PMID:Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line. 138 31

R1-20, a novel mAb reacting with a cell surface Ag on normal human lymphocytes and leukemic cell lines, was shown to induce homotypic cell aggregation in leukemic cell lines. This phenomenon was specific to mAb R1-20 because antibodies recognizing CD2, CD7, CD28, and HLA-ABC failed to exhibit homotypic cell aggregation. Induction of aggregation by mAb R1-20 occurred at 37 degrees C, but not at 4 degrees C and required cytoskeletal integrity. Sodium azide, a metabolic inhibitor, had no effect on the aggregation. Distinct from lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 interaction in which divalent cations are essential elements, R1-20-mediated aggregation was not abolished with EDTA treatment. The R1-20 Ag was determined as a molecule of M(r) 100 to 110 kDa in immunoprecipitation and immunoblotting methods, under both reducing and nonreducing conditions. The molecular composition is quite different from that of any known integrin molecule. The R1-20 Ag was expressed on resting and activated T Lymphocytes as well as on normal B lymphocytes. Monocytes and granulocytes had no detectable R1-20 Ag. Among the leukemia-derived cell lines we used, mAb R1-20 reacted with 18 of 32 T cell lines, 2 of 20 B cell lines, 2 of 3 non-T-non-B cell lines, 2 of 7 myelomonocytic cell lines, and 2 of 3 nonlymphoid-nonmyeloid cell lines. All EBV-transformed B cell lines examined (10 cell lines) were R1-20+. The spectrum of reactivity among the cell lines tested was different from that of known antiadhesion antibodies tested. All these findings indicate that the Ag recognized by mAb R1-20 may represent a new type of cell adhesion molecule.
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PMID:R1-20, a novel monoclonal antibody reacting with a molecule distinct from integrin family, induces homotypic cell aggregation. 160 59

The expression of adhesion molecules on blasts from 14 patients with acute myeloid leukemia (AML) was investigated by immunofluorescence and flow cytofluorometry. All tested blast populations expressed CD18/CD11a complex [leukocyte function antigen-1 (LFA-1)] and CD29 (very-late antigen (VLA)) and the majority were positive for CD54 [intercellular adhesion molecule-1 (ICAM-1), 78.6%] and CD56 [neural cell adhesion molecule (NCAM), 64.3%]. The expression of two other alpha chains of CD18/CD11b and CD11c varied considerably (64.3% and 42.8% of positive cases, respectively). Only one case (AML-M4) showed a weak expression of the activated platelet antigen CD41b. None of the tested blasts expressed the vitronectin receptor (CD61/CD51). No significant correlation between the expression of adhesion molecules and the FAB type of leukemia could be found. All tested blast populations were completely resistant to NK-mediated cytotoxicity and relatively resistant to LAK-mediated cytotoxicity in the standard 51Cr release assay. While no statistically significant correlation of the results in cytotoxicity assays with the expression of adhesion molecules or the expression of HLA-DR antigen could be observed, 2 out of 3 completely resistant cases lacked ICAM-1. These results show that even leukemic blasts which express all of the tested adhesion molecules can still be resistant to LAK-mediated cytotoxicity.
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PMID:Resistance of leukemic blasts to lymphokine activated killer (LAK)-mediated cytotoxicity is not related to their adhesion properties. 171 15

The intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor to three patients with leukemia who were receiving marrow aplasia-inducing chemotherapy resulted in the development of wide-spread erythematous macules and papules. The course of the eruption paralleled the time of infusion of the granulocyte-macrophage colony-stimulating factor. Skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes, increased number and size of dermal macrophages, mild to moderate epidermal exocytosis, intercellular edema, and rare dyskeratotic keratinocytes. Immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule-1 expression. Administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin, resulting in the expression of a cutaneous eruption.
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PMID:Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption. 182 45

We have investigated the precise distribution of human B-lymphocyte subpopulations (CD5+ B lymphocyte, Leu-8+ lymphocyte, immunoglobulin D (IgD)+ lymphocyte, alkaline phosphatase (ALPase)+ B lymphocyte and bcl-2 protein+ B lymphocyte) within the mantle zones (MZs) and phenotypic characterization of human CD5+ B lymphocytes using immunohistochemical techniques and flow cytometric analysis. IgD+ lymphocytes and ALPase B lymphocytes were confined to the inner layer and outer layer of the MZs of secondary follicles, respectively. CD5+ B lymphocytes and Leu-8+ B lymphocytes were mostly located in the inner layer of the MZs. Bcl-2 protein+ B lymphocytes were seen throughout the MZs. The precise distribution pattern of human B-lymphocyte subpopulations may help further understanding of the histogenesis and features of B-cell lymphomas, particularly mantle cell-derived lymphomas as well as the B-cell differentiation pathway. A minor population of CD5+ B lymphocytes expressed IgD. Almost all the CD5+ lymphocytes did not express ALPase. The data support the fact that CD5+ B lymphocytes are located more in the inner layer than in the outer layer of the MZs. Leu-8 and bcl-2 protein were detected in a large population of CD5+ B lymphocytes. In addition, Ki-67 antigen was not expressed on the CD5+ B lymphocytes. The data suggest that human CD5+ B lymphocytes may be long-living and resting (G0 and G1a stage) cells possessing the capability of continuously recirculating between blood and lymph nodes to participate in some immune responses. Moreover, Leu-8 and CD44 were detected in the majority of CD5+ B lymphocytes but intercellular adhesion molecule-1 (ICAM-1) and very late antigen-4 (VLA-4) were detected in the minority. The data may account for a high percentage of Leu-8 and CD44 expression and a low percentage of ICAM-1 and VLA-4 expression on B-chronic lymphocytic leukemia (B-CLL), which is considered to be a neoplastic counterpart of normal CD5+ B lymphocyte.
Leukemia 1994 Jun
PMID:Phenotypic characterization of human B-lymphocyte subpopulations, particularly human CD5+ B-lymphocyte subpopulation within the mantle zones of secondary follicles. 751 26

THP-1 myelomonocytic leukemia cells cultured with either macrophage colony-stimulating factor (M-CSF) or interferon-gamma (IFN-gamma) alone produce, at best, only low levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). However, combinations of the two factors resulted in at least 3- to 20-fold greater amounts of IL-1 beta and TNF-alpha than would have been predicted by additive mechanisms. This enhanced cytokine production was observed when M-CSF and IFN-gamma were added simultaneously or when M-CSF was added 24 h after addition of IFN-gamma to the cells. Similar results were obtained with fresh human peripheral blood cells treated with IFN-gamma + M-CSF. Cycloheximide treatment of the cultures containing M-CSF and IFN-gamma inhibited the production of IL-1 beta and TNF-alpha. Northern blotting studies revealed no effect of IFN-gamma alone on IL-1 beta or TNF-alpha mRNA production. IL-1 beta and TNF-alpha mRNA expression was observed at 2 and 6 h after treatment with M-CSF or IFN-gamma + M-CSF. Higher TNF-alpha mRNA expression was observed at 2 and 6 h after treatment with IFN-gamma + M-CSF, and higher IL-1 beta mRNA expression was observed at 2 h after treatment with IFN-gamma + M-CSF compared with mRNA levels observed for cells cultured only with M-CSF. These results suggest that the augmented cytokine production resulting from treatments with combinations of M-CSF and IFN-gamma occurs due to increased cytokine mRNA and increased cytokine protein synthesis. In addition to up-regulating cytokines, combinations of IFN-gamma and M-CSF resulted in augmented cell surface expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. This was accompanied by morphological and functional changes that included plastic adherence, extensive homotypic aggregation, and a macrophage-like appearance. These phenotypic changes and enhancements in cytokine expression and cell surface molecule expression may be related to activation of monocytic cells to become cytotoxic effectors by M-CSF and IFN-gamma combinations. In vitro cytotoxicity against A-375 melanoma cells was greatest for cultures that contained M-CSF and IFN-gamma in combination.
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PMID:Activation of cytokine production and adhesion molecule expression on THP-1 myelomonocytic cells by macrophage colony-stimulating factor in combination with interferon-gamma. 759 61


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