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 49-year-old man with t(8; 21) acute myeloid leukemia relapsed 8 months after successful induction chemotherapy with a paraspinal granulocytic sarcoma. There was no evidence of leukemia in the bone marrow at relapse. At initial presentation, the blasts co-expressed CD 15, CD 33, CD 34, CD 45, CD 19, and CD 56 (a neural cell-adhesion molecule). Expression of certain cell-adhesion molecules on leukemic blasts may determine a tendency to develop extramedullary relapse. The co-expression of CD 56 may have a role in the predisposition of t(8; 21) AML to develop GS.
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PMID:Neural cell-adhesion molecule (CD 56)-positive, t(8;21) acute myeloid leukemia (AML, M-2) and granulocytic sarcoma. 752 61

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

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.
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PMID:Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro. 766 73

Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/ lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.
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PMID:CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics. 766 44

NK cells can recognize and lyse target cells without restriction by the MHC. The molecular interaction responsible for NK cell recognition is poorly understood. It has been frequently suggested that the loss of beta 2 integrin in immune competent cells may lead to dysfunction due to inadequate cell-cell interaction. We examined the role of lymphocyte functional adhesion molecule-1 in the function of a human natural killer leukemia cell line, YT-1. A mutant YT-1(-) cell subclone showed an absence of killing activity against a B lymphoma cell line, compared with that against a CD11a/CD18 positive parental cell line, YT-1(+) cells. We found that this loss of cytotoxicity was correlated with lack of surface expression of CD11a/CD18 molecules due to the mutation of the CD18 gene. Using gene transfer experiments, we provide strong evidence demonstrating that CD18 transfection to this mutant NK cell line, YT-1(-), restored the surface expression of CD11a/CD18, and this restoration was accompanied by reexpression of cytotoxic function.
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PMID:Restoration of lytic function in a human natural killer cell line by gene transfection. 791 Oct 75

High-dose recombinant human Interleukin-2 was given to 21 patients with acute myeloid (n = 11) or lymphoid (n = 10) leukemia in relapse. A rapid decrease in the peripheral leukemic blasts numbers was observed in six patients. We were unable to demonstrate at the bone marrow level a diminution in the percentage of leukemic blasts. However an increase in the expression of the adhesion molecule CD54/ICAM-1(LFA-1 ligand) affected the leukemic bone marrow blasts of these six patients. This increase in CD54 was found in eight of the 11 (73%) AML and four out of the ten (40%) ALL blasts and CD58/LFA-3 (CD2 ligand) to a lesser extent. This increased expression was not associated with modifications in the expression of MHC class II molecules. In vivo IL-2 also dramatically modified the bone marrow T-cell subsets via the increase of CD3+ cells expressing the CD45RO 'memory' marker (six out of the eight tested patients) or CD54 (seven out of the eight tested patients). Altogether these results demonstrate that leukemic blasts can be affected by in vivo IL-2 via mechanisms that could involve T cells.
Leukemia 1994 Jul
PMID:Modifications of leukemic blast cells induced by in vivo high-dose recombinant interleukin-2. 803 17

Clinical studies indicated an enhanced antileukemic effect of allogeneic bone marrow transplantation (BMT), as compared with autologous BMT. After allogeneic HLA-identical BMT, donor-derived cytotoxic T lymphocytes (CTLs) directed at minor histocompatibility (mH) antigens on the recipients, tissues can be shown. To evaluate the antileukemic reactivity of mH antigen-specific CTLs, we analyzed the expression of mH antigens on circulating lymphocytic and myeloid leukemic cells. We show that the defined mH specificities HA-1 through HA-5 and H-Y are present on leukemic cells, indicating that mH antigen-specific CTLs are capable of HLA class I-restricted antigen-specific lysis of leukemic cells. Compared with interleukin-2-stimulated normal lymphocytes, leukemic cells of lymphocytic origin are less susceptible to T-cell-mediated cytotoxicity by the HA-2 mH antigen-specific CTL and the anti-HLA-A2 CTL clone. A possible explanation for this phenomenon is impaired expression of the LFA-1 adhesion molecule. Our study suggests that mH antigen-specific HLA class I-restricted CD8+ CTLs may be involved in the graft-versus-leukemia reactivity after allogeneic BMT.
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PMID:Recognition of minor histocompatibility antigens on lymphocytic and myeloid leukemic cells by cytotoxic T-cell clones. 811 Oct 46

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

Graft-vs.-leukemia (GVL) is postulated to be the principal mechanism responsible for continued remission after allogeneic bone marrow transplantation (BMT). The specific cytotoxic effectors mediating this effect are as yet undefined, but the major histocompatibility complex (MHC)-nonrestricted lysis of tumor cell lines by natural killer (NK) and lymphokine-activated killer (LAK) cells from recipients of allogeneic BMTs has been proposed as an in vitro correlate of GVL. In vitro culture or treatment in vivo with interleukin-2 (IL-2) is associated with enhanced NK cytotoxicity and lysis of NK-resistant targets (LAK cytotoxicity). NK, LAK, and cytotoxic T lymphocytes (CTL) have cytotoxic properties against autologous and allogeneic leukemic targets. These immune effector cells require receptor-ligand interaction for target recognition and adhesion via specific molecules such as integrins, a group of heterodimeric transmembrane glycoproteins. The integrins include the very late activation (VLA) subfamily, which all share the same beta 1 subunit but have distinct chains. VLA-6 (CDw49f) has been identified on NK cells and binds to laminin, a basement membrane protein found on malignant tumor cells but not normal cells. Monoclonal antibodies (mAbs) to laminin have been found to inhibit in vitro cytotoxicity of the tumor cell line K562, suggesting an important role for VLA-6 in this interaction. The specific aim of this study was to investigate the role of VLA-6 in the interactions of the tumor cell lines K562 and Daudi with peripheral blood lymphocytes (PBL) acting as effectors in cell-mediated cytotoxicity from normal volunteers, patients recovering from chemotherapy, and patients recovering from autologous or allogeneic BMT. In over 96% of assays, incubation of effector cells with anti-CDw49f mAbs led to detectable inhibition of NK and LAK cell-mediated cytotoxicity. More notably, the degree of anti-VLA6-induced suppression of LAK activity was significantly greater in the normal donors than in any of the patient groups, despite a significantly lower incidence of expression of VLA-6 on NK cells from controls than from patients. This implies a reduced role for this adhesion molecule in LAK activity following some form of in vivo stimulation. This hypothesis is supported by the observation that addition of exogenous IL-2 to the cultures ameliorated the effect of VLA-6 blockade, although the incidence and level of VLA-6 expression was unchanged by IL-2. In contrast, VLA-6 blocking led to a greater reduction in NK activity of BMT recipients than of normal donors, demonstrating that the VLA-6 adhesion pathway is important in this group of patients. These results indicate that the VLA-6-laminin interaction is important in normal NK-target interaction but may play a less significant role in the innate cytotoxic response post-BMT, perhaps reflecting subtle differences in the subsets of NK cells present in BMT recipients compared with normal donors.
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PMID:VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation. 854 43

Integrins are central to many aspects of the tissue localization of normal and malignant lymphocytes. We examined how integrin function, rather than simple expression, might determine disease behavior in chronic lymphocyte leukemia (CLL). Using fluorescence-activated cell sorting (FACS) and immunoprecipitation, we first established the precise integrin heterodimer expression of a representative group of CLL patients (beta1 consistently present, with variable alpha 3, alpha 4, and alpha 5; alpha 4 beta 7 often expressed; alpha L beta 2 high; alpha V beta 3 absent). Regarding function, we initially examined the ability of CLL cells to interact with endothelium, because such interaction is the initial event determining the entry of CLL lymphocytes into tissues. The abnormal lymphocytes were shown to bind at low levels to unstimulated endothelium via beta 2/intercellular adhesion molecule (ICAM). However, when the endothelium was stimulated, markedly enhanced interaction with endothelium was observed in approximately half the cases; in these patients, the neoplastic population expressed alpha 4 beta 1, which conferred the ability to adhere strongly to stimulated endothelium via the alpha 4 beta 1 ligand, vascular cellular adhesion molecule-1 (VCAM-1). In relation to the migration of CLL cells within tissues, the abnormal lymphocytes showed differential binding to various adhesive proteins; they did not attach to basement membrane components, but displayed variable adhesion to fibronectin (FN). Finally, we examined the role of cell activation in these processes, and showed that activated CLL lymphocyte populations showed an increased capacity to adhere to both endothelium and matrix. Moreover, ex vivo CLL cells showed no capacity to migrate through endothelium/stroma, but were able to do so after cytokine stimulation. These studies show how the constitutive integrin expression/function, the intrinsic activation state of the cell, and the capacity of cytokines to modify integrin-mediated function all combine to determine the different patterns of clinical disease observed in CLL.
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PMID:Integrin function in chronic lymphocytic leukemia. 863 49


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