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)

Acute myeloid leukemia (AML) cells express the surface adhesion proteins intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function associated molecule-3 (LFA-3, CD58). Exposure to the myeloid growth-promoting cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates expression of ICAM-1 and LFA-3 on AML cells but does not increase their sensitivity to lysis by interleukin-2-activated natural killer cells (LAK) in 51Cr assays. However when AML cells are exposed to GM-CSF prior to incubation with LAK, their subsequent clonogenic activity is significantly reduced. If a blocking antibody to ICAM-1 is added during the incubation period of AML with LAK, the inhibitory effect is completely ablated. A less pronounced effect is observed with an antibody to LFA-3. ICAM-1 is expressed on a greater proportion of CD34+ than CD34- AML cells and exposure to GM-CSF induces a significantly greater upregulation of ICAM-1 on leukemic CD34+ cells than their CD34- counterparts. These data suggest that the inhibitory effect of IL-2-activated natural killer cells on clonogenic AML cells is mediated principally via the lymphocyte function associated molecule-1 (LFA-1)/ICAM-1 interaction. Interleukin-2 upregulates LFA-1 expression on natural killer cells. Simultaneous administration of effector cell activators such as IL-2 and target cell modulators such as GM-CSF may have a therapeutic benefit in patients with minimal residual myeloid leukemia.
Leukemia 1995 Apr
PMID:GM-CSF enhances IL-2-activated natural killer cell lysis of clonogenic AML cells by upregulating target cell expression of ICAM-1. 772 3

The immune response to a murine myeloid leukemia (cell line C1498) was studied in vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function antigen-1 (LFA-1) on effectors and intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target cells. However, the ability of nonimmunized mice to resist an in vivo challenge of a low dose (10(4)) of C1498 was NK-cell, but not T-cell dependent. The failure of T cells to participate in the immune surveillance of a low leukemia burden appeared, in part, because of a lack of expansion of leukemia reactive CTL precursors (CTLp). Leukemia reactive CTLp frequency estimations in naive and leukemia bearing mice were not significantly different (range, 1:20,600 to 1:74,000) in contrast to immunized mice (range, 1:1,400 to 1:4,400). Leukemia reactive CTLp could be expanded to a level that could apparently mediate in vivo immune surveillance of 10(5) leukemia cells by injection of irradiated leukemia cells intraperitoneally (IP) or subcutaneously (SC), but not intravenously (IV). However, IV injection of 10(5) live leukemia cells engineered to secrete interleukin-2 (IL-2) resulted in systemic immunity mediated primarily by CD8+ T cells. We conclude that NK cells can mediate immune surveillance of a low leukemia burden. CD8+ CTL-mediated immune surveillance can eliminate a higher leukemia burden than NK cells, but requires T-cell help, which can be delivered by local IL-2. Both NK and CTL-mediated immune surveillance of C1498 murine myeloid leukemia is dependent on recognition through the LFA-1:ICAM adhesion pathway.
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PMID:Dependency on intercellular adhesion molecule recognition and local interleukin-2 provision in generation of an in vivo CD8+ T-cell immune response to murine myeloid leukemia. 772 79

Cutaneous lesions of T-cell proliferative disorders are characterized by epidermotropic infiltration of the neoplastic cells and expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR by lesional keratinocytes. Using cloned HTLV-1-infected T-cells obtained from patients with adult T-cell leukemia (ATL), we have studied immunobiological activities of cytokines released from the T-cell lines and their ability to adhere to cultured keratinocytes. Three out of the five CD-4-positive, HTLV-1-infected T-cell clones secreted both IFN-gamma and IL-4, similar to murine Th0 clones. The other two clones did not produce such cytokines. ICAM-1 and HLA-DR molecules were induced on cultured normal human keratinocytes and organ-cultured skin specimens by co-cultivation with IFN-gamma-producing T-cell clones or their culture supernatants. Induction of both molecules was markedly inhibited by pretreatment of the supernatants with excess amounts of anti-IFN-gamma monoclonal antibody. The number of cells adherent to the normal cultured keratinocytes was greater in the IFN-gamma-producing clones than in the non-producing ones. These data suggest that some HTLV-1-infected clones produce cytokines, including IFN-gamma, which in turn induce ICAM-1 on keratinocytes, thereby enhancing the ability of the T-cell clones to adhere to the keratinocytes.
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PMID:Induction of intercellular adhesion molecule-1 and adherence of HTLV-1-infected T-cells to cultured keratinocytes. 791 43

Adhesion between leukemic cells and the vascular endothelium has been suggested to play a role in the development of leukostasis in myelocytic leukemia. To define the role of adhesion molecules on the surface of endothelial cells in leukostasis, we used immunohistochemistry to study the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in lung tissue of 4 patients with pulmonary leukostasis. Lung tissue of 2 patients with myelocytic leukemia without leukostasis and 4 patients with irrelevant nonpulmonary disease was used as a negative control. Positive control tissues included a lymph node with angioimmunoblastic lymphadenopathy and a hyperplastic tonsil. Weak positive staining for ELAM-1 was found in 1 patient in vessels, both with and without leukostasis. Expression of VCAM-1 and ICAM-1 in all patients tested was similar to that in the negative controls. The results of this study suggest that activation of endothelium, with increased expression of the endothelial adhesion molecules under study, is not a prerequisite for the development of pulmonary leukostasis in leukemia.
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PMID:Endothelial activation antigens in pulmonary leukostasis in leukemia. 823 71

A mouse monoclonal IgG1 antibody, referred to as NI-58, has been produced. In immunofluorescence assay, this antibody reacted with myelomonocytes, EBV-B cells, Burkitt's lymphoma cells, T cell leukemia cells and peripheral blood mononuclear cells, but not with erythroid cells. The surface antigen on U937 cells recognized by NI-58 had a molecular size of 65 kDa as determined by immunoblotting analysis. As a biological function, NI-58 strongly inhibited the homotypic cell adhesion of LPS-stimulated U937 cells. It was found that the antigen defined by NI-58 was distinct from CD54 (intercellular adhesion molecule-1) in it's pattern of cellular expression and molecular weight, suggesting that NI-58 recognizes a new adhesion molecule and inhibits the homotypic cell adhesion of LPS-stimulated U937 cells.
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PMID:[Establishment of monoclonal antibody NI-58 which inhibits homotypic cell adhesion of LPS-stimulated U937 cells]. 831 9

In order to understand the variety of HTLV-1-associated cutaneous diseases, we studied the cytological profile of HTLV-1-infected T-cell lines established from patients with adult T-cell leukaemia (ATL). Among four CD4+ cell lines, termed 16T(-), 35T(-), MH-1, and KS-2, the 16T(-) cells secreted elevated quantities of IL-4, IL-6 and IFN-gamma and expressed mRNA for each cytokine in the absence of exogenous stimulation. The 35T(-) cells secreted IL-6 and a small amount of IFN-gamma, but not IL-4. The MH-1 and KS-2 cells secreted only IL-6 in the absence of stimulation. In response to stimulation with phorbol-12-myristate-13 acetate (PMA), the 16T(-) cells produced more IL-4 and IFN-gamma, whereas the 35T(-) and MH-1 cells exhibited increased secretion of IFN-gamma, but still no IL-4 or IL-4 mRNA production. Although neither IL-4 nor IFN-gamma were found in the culture supernatant of KS-2 cells, the production of IL-4 mRNA was detected by RT-PCR. Culture supernatants from the 16T(-) and 35T(-) cells induced the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR by cultured keratinocytes. This response was inhibited by pretreatment of the supernatant with anti-IFN-gamma antibodies. These results indicate that some HTLV-1-infected T-cell lines constitutively secrete various cytokines, including biologically active IFN-gamma. The diversity of immunobiological functions of the T-cell lines may be related to the variety of clinical features present in ATL patients.
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PMID:Diversity of immunobiological functions of T-cell lines established from patients with adult T-cell leukaemia. 854 36

In this study, we examined expressions of several adhesion molecules (AdMs), i.e. leukocyte function antigen-1 (LFA-1: CD11a/CD18), Hermes homing receptor (CD44) and intercellular adhesion molecule-1 (ICAM-1: CD54), on leukemia cells from 51 adult patients with newly diagnosed acute myeloid leukemias (AMLs) to elucidate clinical significance of these AdM expressions. Those expressions in lymphoid malignancies have been correlated with tumor evolutions, but CD44 was detected in all the AML cases examined and CD54 expression did not associate with their clinical characteristics or outcomes. However, we found that LFA-1 expressions significantly correlated with splenomegaly, resistance to induction chemotherapies and short survival periods in AML patients.
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PMID:Clinical significance of LEA-1 expression in adult acute myeloid leukemia. 864 44

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expressed mainly by activated T cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, regarded as the malignant components of Hodgkin's disease (HD), display high levels of the counter-receptors for these ligands, ie CD30, CD40 and 4-1BB. CD30L and CD40L are known to share some biological activities that can be linked to the unbalanced secretion of cytokines seen in HD. In addition, cell contact-dependent molecules such as adhesion or activation antigens are critically involved in T cell/H-RS cell interactions. Primary and cultured H-RS cells frequently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD40L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells on the mRNA and protein level, as a result of transcriptional gene activation. Furthermore, enhanced CD54 surface expression by these cells is accompanied by increased shedding of surface-bound CD54, as evidenced by high levels of the 82 kDa soluble (s) CD54 form detectable in culture supernatants after specific stimulation. Addition of CD30L in combination with CD40L to cultured H-RS cells additively enhanced CD54 surface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.
Leukemia 1996 May
PMID:The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. 865 79

We have found that pretreatment of a human oral mucosal epithelial cell line KB with natural human interferon-alpha (IFN-alpha) augments the expression of intercellular adhesion molecule-1 (ICAM-1), and the complex of CD29 and CD49b, which is known as very late antigen (VLA)-2, in a dose-dependent manner, whereas the expression of other adhesion molecules such as CD44 leukocyte function associated antigen-3 (LFA-3), VLA-4 and endothelial leukocyte adhesion molecule-1 (ELAM-1) did not show any significant changes under the same conditions. The pretreatment of KB cells with IFN-alpha also induces the adhesion of these cells to the human leukemia T cell line MOLT-16 and to peripheral T lymphocytes in a dose-dependent manner. However, the adhesion of the above-mentioned T cells to KB cells was not inhibited by specific antibodies against ICAM-1, CD29, and CD49b. The results thus show that adhesion molecules other than ICAM-1, CD29, AND CD49b are responsible for the induced adhesion between T cells and IFN-alpha-pretreated KB cells.
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PMID:Natural human interferon-alpha enhances the expression of intracellular adhesion molecule-1, integrin alpha 2 and beta 1 by a mucosal epithelial cell line. 871 71

8-Methoxypsoralen (8-MOP) plus long-wavelength UV radiation (UVA, 320-400 nm) have been used to treat various diseases such as cutaneous T-cell lymphoma, systemic scleroderma, rheumatoid arthritis and rejection of heart transplants. However, the immunological mechanism of this treatment remains unknown. In this report, we investigated the effect of 8-MOP/UVA on the modulation of the immunogenicity of a T-cell leukemia cell line (RL male 1 cells). The results demonstrated that the stimulator function of the in vitro 8-MOP/UVA-treated RL male 1 cells was enhanced in both RL male 1-specific allogeneic and syngeneic immune responses. Furthermore, the enhancement of the immunogenicity of the 8-MOP/UVA-treated RL male 1 cells was found to be strongly associated with the increase of intercellular adhesion molecule-1 expression on these 8-MOP/UVA-treated tumor cells. Therefore, our findings suggested that the alteration of the expression of the immune-related cell surface molecules might be an important effect of 8-MOP/UVA treatment on the elevation of the immunogenicity of the 8-MOP/UVA-treated tumor cells.
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PMID:The immunological effect of 8-methoxypsoralen and UVA treatment on murine T-cell leukemia. 880 36


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