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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The killing of human leukemia cells by cloned human LAK cell was investigated with 51Cr release, semisolid agar colony-formation and MTT assay. Human LAK cells were generated and cloned from normal peripheral blood mononuclear cells stimulated with IL-2. Cloned LAK cells showed significant cytotoxicity against human erythroleukemia cell line K 562, promyelocytic leukemia cell line HL 60 and T-lymphoblastic leukemia cell line Jurkat in standard 4-hr 51Cr release assay and the lytic percentage were 67.1%, 58.4% and 53.1% with E/T ratio of 40:1. Moreover, cloned LAK cells could also inhibit the 6-day spontaneous colony-formation of K 562 and HL 6 C cells in semisolid cultures when the LAK cells were preincubated with target cells for 4 hours in liquid medium at 37 degrees C. The degree of colony inhibition was 91% for K 562 and 96% for HL 60, which was quantitatively greater than that determined by 51Cr release at the same E/T ratio of 40:1. In addition, with MTT assay, cytotoxicity of supernatant of cloned LAK cells 3 days in culture against K 562 and HL 60 cells was observed. Our data indicated that cloned human LAK cells could kill both human leukemia cells and their stem cells and the mechanism may involve direct lysis and/or inhibition mediated by LAK cells and indirect inhibition of some soluble factors released from LAK cells.
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PMID:[Mechanism of cloned human lymphokine-activated killer (LAK) cells killing human leukemia cells in vitro]. 139 52

In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.
Leukemia 1992 Oct
PMID:Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells. 140 55

We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2R alpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2R alpha at 24 h after induction by IL-6 is strongly enhanced by IL-1. However, IL-1 does not change the transient kinetics of expression of IL-2R alpha. Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1. By Northern analysis, we find that the increase in IL-2R alpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2R alpha but not IL-2R beta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2R alpha mRNA expression is due to both an increase in IL-2R alpha gene transcription and to an increase in IL-2R alpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2R alpha can be specifically up-regulated by IL-1, however, without affecting the transient nature in expression of IL-2R alpha.
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PMID:Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism. 142

Interleukin-2 receptors are composed of at least two polypeptide chains of alpha (55KD) and beta (75KD). The IL-2R beta chain is an essential component of the functional receptor for signal transduction of IL-2. We previously reported the distribution of IL-2R subunits among peripheral blood mononuclear cells. We here present some data regarding the expression of IL-2R subunits on various hemopoietic malignant cells. Fresh leukemic cells obtained from adult T cell leukemia patients expressed both alpha and beta chains, and leukemic cells derived from some patients with T cell leukemia, B cell leukemia or myeloid leukemia expressed the alpha and/or beta chain of IL-2R. The IL-2R beta chain on these leukemic cells were demonstrated to be functional for cell growth signaling. IL-2R alpha and beta chains should be tumor markers.
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PMID:[The expression of IL-2 receptor subunits on various leukemic cells]. 144 19

Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations.
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PMID:Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells. 146 Feb 93

Lymphokine activated killer cells have potent antitumor effect both in vitro and in vivo. They have been reported to suppress bone marrow (BM) progenitor cell activity (PCA) in vitro, thus raising concern about the feasibility of their use after autologous bone marrow transplantation. The present study was carried out to evaluate the effect of LAK cells on BM engraftment in a syngeneic BMT setting in mice. LAK cells supplemented with or without exogenous interleukin-2 therapy did not impair the hematopoietic reconstitution or survival of mice undergoing BMT. LAK cells also did not reduce the PCA of the engrafted BM. LAK cell therapy did not cause graft-versus-host disease. Finally, LAK cells supplemented with IL-2 therapy improved the graft-versus-leukemia effect. These findings suggest that LAK cells plus IL-2 therapy after BMT does not impede hematopoiesis and should be evaluated as an adjuvant therapy with the aim of eradication of minimal residual disease after autologous BMT.
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PMID:Lymphokine-activated killer cells in autologous bone marrow transplantation. Evidence against inhibition of engraftment in vivo. 146 68

The production of interleukin 1 (IL-1) by lipopolysaccharide (LPS)-stimulated myelomonocytic cell lines ML-1, THP-1 and PL-21 was significantly enhanced by the addition of insulin, insulin-like growth factor (IGF)-I or IGF-II into the cell cultures. The IL-1 activity in the supernatants from cell cultures stimulated with LPS and insulin was completely neutralized by anti-IL-1 beta antibody. Anti-IL-1 alpha antibody had no inhibitory effect. Insulin itself did not stimulate IL-1 beta production directly, but increased it in the mitogen activated cells. However, insulin had no enhancing effect on the production of IL-1 alpha by human T cell lymphotropic virus-I (HTLV-I)-infected T cell lines or on IL-2 production by mitogen-stimulated leukemia T cell lines. Thus, insulin and its related cytokines are shown here as other molecules selectively modulating the production of IL-1 beta in myelomonocytic cell lines.
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PMID:Selective enhancement of interleukin 1 beta production in myelomonocytic cell lines by insulin and its related cytokines. 148 10

The Tax1 protein of human T cell leukemia/lymphoma virus type I (HTLV-I) has been shown to stimulate the proliferation of human lymphocytes. Here we report that lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha-chain (IL-2R alpha) expression in human lymphocytes. Functional activation of IL-2R alpha expression in peripheral blood lymphocytes treated with Tax1 was demonstrated using an [125I]IL-2-binding assay. In addition, an enzyme-linked immunosorbent assay demonstrated that soluble IL-2R alpha in the medium of IL-2- and Tax1-treated cells was over 13-fold greater than in the medium of control treated cells. Overexpression of IL-2R alpha is a common clinical feature of some patients with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myopathy (TSP/HAM). The ability of extracellular Tax1 protein to activate expression of IL-2R alpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed in both ATL and TSP/HAM.
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PMID:Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis. 150 87

We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2.
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PMID:[Large granular lymphocytic leukemia]. 151 40

Despite major advances, graft-versus-host disease (GVHD) remains a major obstacle to clinical bone marrow transplantation. Prophylaxis by T cell depletion is associated with increased rates of engraftment failure and leukemic relapse. Treatment with high-dose IL-2 can markedly protect lethally irradiated mice from GVHD-related mortality, especially when T cell-depleted (TCD) syngeneic bone marrow cells (BMC) are co-administered. In these IL-2-protected animals, allogeneic reconstitution is observed, and a graft-versus-leukemia effect of allogeneic T cells is preserved. To determine whether IL-2 might increase alloresistance under conditions in which alloengraftment is more difficult to achieve, we have now evaluated the possible effect of IL-2 on: (1) competitive repopulation of lethally irradiated mice by mixtures of TCD allogeneic and TCD syngeneic BMC; (2) radiation protection by TCD allogeneic BMC; (3) timing of hematologic recovery; and (4) allogeneic engraftment in sublethally irradiated recipients. The results show that IL-2 has only a limited and strain-restricted effect on alloengraftment. This effect may reflect activation of alloresistant host natural killer cells, a cell population which is not essential for the protective effect of IL-2 against GVHD.
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PMID:Alloengraftment in IL-2-treated mice. 152 5


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