Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were carried out to investigate whether the human T-lymphotropic virus type I (HTLV-I), alone or in combination with a chemical mutagen such as mitomycin C (MMC), has the capacity to damage host chromosomes. Cord-blood T lymphocytes (CBL) were infected by co-cultivation with lethally irradiated HTLV-I-producing cells. Infected and immortalized CBL were then studied for frequencies of sister chromatid exchanges (SCE), chromosome breaks and micronuclei. HTLV-I-infected cells had statistically higher baseline SCE, chromosome aberrations and micronucleus values than the uninfected control CBL. While MMC treatment further augmented these values both in control and in infected lymphocytes, the latter did not show dose-related increases, most likely because of the more pronounced MMC-induced delaying effect on cell progression to mitosis. In view of similar previous observations in mouse lymphocytes carrying the Moloney murine leukemia virus, it is suggested that expression of a common retrovirus gene product, such as the pol endonuclease, might be responsible for the cytogenetic abnormalities observed. In addition to the IL-2 autocrine loop, the direct induction of chromosome damage by HTLV-I in target lymphocytes may be related to the pathogenesis of malignancies associated with HTLV-I infection.
Leukemia 1988 Dec
PMID:Chromosome damage induced in cord blood T-lymphocytes infected in vitro by HTLV-I. 326 65

Lymphokine-activated killer (LAK) cells were grown from C57BL/6 mouse spleen cells by culturing the cells with recombinant human IL-2 (r-IL-2). The unlabeled or [3H]uridine-labeled LAK cells were enclosed in a diffusion chamber, which was implanted into the peritoneal cavity of a syngeneic mouse, and the mouse was treated with an i.p. injection of r-IL-2 or saline (control). In order to detect the activity of administered r-IL-2, the diffusion chambers were taken out from the mice 20-40 h after the implantation, and the viability and cytotoxic activity of LAK cells in the chambers were determined by measuring the radioactivity of the cells and their cytotoxicity to EL 4 mouse leukemia cells respectively. When the mice were treated with saline, the radioactivity of LAK cells was greatly decreased. However, when the mice were treated with r-IL-2, the radioactivity of LAK cells was sustained. An i.p. administration of IL-2 also prevented any decrease in the cytotoxic activity of LAK cells.
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PMID:Use of Millipore diffusion chambers to assay in vivo IL-2 activity. 387 15

In human long-term marrow cultures granulomonopoiesis is maintained for several weeks. Studies on granulomonocytic progenitors (CFU-GM) and their progeny have shown that survival, proliferation, differentiation and maturation of these cells are controlled by a set of glycoproteins, the colony-stimulating factors (CSFs) and the Steel factor. We have studied the expression of these factors using reverse transcriptase polymerase chain reaction (RT-PCR) in 17 adherent layers of normal bone marrow at 3, 5 or 7 weeks of culture. We have taken the 5637 bladder carcinoma cell line as a control for expression of GM-CSF, M-CSF, G-CSF and Steel factor, and PHA-activated T lymphocytes as a control for expression of multi-CSF (interleukin 3, IL-3). We have found that GM-CSF was expressed in the 17 adherent layers without induction by interleukin 1 beta (IL-1 beta). M-CSF was also detected in all cases, but in two early-stage (week 3 and week 5) cultures only after stimulation by IL-1 beta. G-CSF was detected in only 11 cases (three without IL-1 beta, and eight after addition of IL-1 beta). Steel factor was detected in 14 cases (ten without IL-1 beta, and four after addition of IL-1 beta). IL-3 was not detected even by means of nested RT-PCR. These data indicate in six late-stage (week 5 or week 7) cultures G-CSF messenger concentrations 10(3)-fold less than in 5637 control cells (for an identical amount of total cellular RNA). A similar conclusion may be drawn for Steel factor in three late-stage cultures. For IL-3 our negative results indicate a messenger concentration 10(5)-fold less than in activated T lymphocytes. These results suggest a crucial role for GM-CSF and M-CSF in the maintenance of granulomonopoiesis in human long-term cultures. The role of G-CSF and Steel factor may be more marginal. Eventually IL-2 may not be involved in the regulatory process.
Leukemia 1994 Mar
PMID:The detection of colony-stimulating factors and steel factor in adherent layers of human long-term marrow cultures using reverse-transcriptase polymerase chain reaction. 751 Mar 57

Cyclopentenone prostaglandins PGA1 and PGJ2 can inhibit the growth of HTLV-1 infected cord blood-derived human mononuclear cells (CBMC), both after acute infection and in chronically infected, immortalized cells. When CBMC were exposed to HTLV-1 infection by coculturing with lethally irradiated, virus-donor allogeneic MT-2 cells, they underwent a proliferative response, that peaked within the first week and then declined. PG treatment did not inhibit the initial proliferation (day 4) of cocultured CBMC, while multiple treatments with PGA1 and more efficiently with PGJ2, suppressed the late cell proliferation (from day 8 onward). The pharmacological effects of PGA1 and PGJ2 were reversible and therefore multiple treatments were required to maintain their antiproliferative activity. Increasing concentrations (20, 40, 80 IU/ml) of recombinant IL-2 did not affect the virus-associated proliferative response of CBMC, and exogenous IL-2 did not revert the antiproliferative effect of both PGs. Arrest of proliferation in cocultured CBMC occurred concomitantly with expression of high levels of HSP70 in the cells. In fact, though HSP70 expression was induced early (day 5) after exposure to HTLV-1, its expression was further increased after multiple PG treatments and high levels were found when the antiproliferative effect of PGs became manifest. Since HSP70 protein family is involved in the control of cell cycle as well as in antigen processing and presentation during the immune response against tumor cells and pathogens, the persistent expression of this protein in PG-treated cocultures suggested that, beside inhibiting the growth of virus-infected cells, HSP70 expression might play a role in modulating the immune function of CBMC. However, unlike in most virus infection models, in which cyclopentenone PGs exert clear antiviral effects by inhibiting the synthesis and maturation of virus proteins, no antiviral activity was found in this model of infection. This strongly suggests that the main effect of these PGs against HTLV-1 infected cells consists in inhibiting proliferation in vitro without affecting viral expression.
Leukemia 1994 Jun
PMID:Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1 infection is independent of IL-2 and is associated with HSP70 induction. 751 27

Peripheral blood lymphocytes from bovine leukemia virus (BLV)-negative and BLV-infected, aleukemic cows with persistent lymphocytosis were evaluated for expression of B and T lymphocyte subset-specific molecules and co-expression of the interleukin-2 receptor alpha (IL-2R alpha) molecule. Results demonstrate enhanced mitogen-induced expression of the IL-2R alpha molecule on B lymphocytes from BLV-infected, lymphocytotic cows. Lymphocyte subset analyses further demonstrate that BLV-infected, lymphocytotic cows are not only characterized by sustained elevations in CD5+ B lymphocytes, but also show significantly elevated numbers of CD3+, CD4+, and CD8+ T lymphocytes. These results provide evidence suggesting that B lymphocytes from BLV-infected, lymphocytotic cows are more sensitive to activation signals and up-regulation of the IL-2 signaling pathway than lymphocytes from clinically normal BLV-free cows, and that T lymphocytes may be involved in the aberrant regulatory pathways underlying BLV-induced persistent B lymphocytosis.
Leukemia 1994 Jun
PMID:Enhanced B-lymphocyte expression of IL-2R alpha associated with T lymphocytosis in BLV-infected persistently lymphocytotic cows. 751 28

The high incidence of spontaneous T cell lymphomas in AKR mice (affected by sustained viremia) can be greatly reduced by experimental manipulations including thymus removal at young age or by genetic manipulation changing the Fv-1 allele that controls replication and spread of viruses (establishing the congenic AKR.Fv-1b mice). Although T cell lymphomagenesis is prevented, all these mice were shown to carry endogenous ecotropic provirus-induced potential lymphoma cells (PLCs) in a dormant state. The termination of the dormant state, leading to a high incidence of CD5+ IgM+ B cell lymphomas, was triggered by interference with T cell functions (optimal effect observed following in vivo administration of anti-CD8 moAb), administration of T cell growth factors or by injecting the MCF-247 recombinant virus isolate (from AKR origin) that affects T cell functions. The assumption that the PLC dormant state is maintained through specific immunological mechanisms (involving T cells or antibodies recognizing PLCs) could not be substantiated experimentally. The results of the present studies suggest that T cells provide immunoregulatory signals or factors that contribute to the maintenance of the B cell lymphoma arrest and/or proliferation. Analysis of cytokine levels produced by splenocytes taken from mice during PLC dormancy or its breakdown indicated reduced levels of IL-2 and IL-4 and marked elevation of IL-1 and IL-6 associated with the termination of the dormant state. The effect of IL-1 and IL-6 on terminating the dormant state was demonstrated by injecting these cytokines into PLC carriers, thymectomized 12-month-old AKR mice, yielding 80-85% CD5+ IgM+ B cell lymphomas. The role of IL-6 on B cell lymphoma proliferation was also indicated in MCF-247 mediated termination of dormancy, by inhibiting significantly its effect via in vivo administration of anti IL-6 moAbs.
Leukemia 1995 Jun
PMID:Role of cytokines in termination of the B cell lymphoma dormant state in AKR mice. 759 76

In this study we have demonstrated that natural killer (NK) cells adhere to elements of the bone marrow stroma (BMS) including fibroblasts, fibronectin and laminin but not to collagen type I, vitronectin and hyaluronic acid. NK cells bind to fibronectin and laminin using the beta 1 integrins VLA-4 and VLA-5, and VLA-6 respectively. The mechanism of adhesion to bone marrow fibroblasts is more complicated with beta 1 and beta 2 integrins being partially responsible but the majority of adhesion remaining unexplained. IL-2 stimulation of NK cells resulted in an increase in the expression of adhesion molecules involved in binding of NK cells to bone marrow fibroblasts (BMF) and extracellular matrix (ECM) proteins including the beta 1 chain CD29, alpha chains of VLA-4 and 5, beta 2 chain CD18 and alpha L chain CD11a. A marked increase in expression of beta 7 was also observed. There was a significant increase in the adhesion of NK cells to fibronectin in response to IL-2 treatment. NK cells also bound more strongly to BMF following IL-2 treatment although the development of cytotoxicity appeared to interfere with the adhesion assay. NK cells competitively inhibit the binding of AML blasts but not ALL blasts to BMF. Mechanisms underlying the inhibition of leukemic growth by NK and LAK cells may include direct and cytokine mediated cytotoxicity and perturbation of the interaction of leukemic blasts with the bone marrow stroma which is essential for blast cell survival.
Leukemia 1995 Jun
PMID:Natural killer cells adhere to bone marrow fibroblasts and inhibit adhesion of acute myeloid leukemia cells. 759 92

The interleukin 2 receptor (IL-2R) is composed of at least three different chains that may be variably expressed on normal and neoplastic lymphocytes. While considerable knowledge has been gained on the expression of the IL-2R alpha chain on human leukemic cells of different origin, less is known of the beta and gamma chains. In view of the highly pleiotropic functions exerted by IL-2, the IL-2-IL-2R interactions may play an important role in various leukemias. In this review we focus on the expression and function of the IL-2R complex on human normal and leukemic B cells. Possible implications in the expansion of the neoplastic clone and in the clinical course of the disease are discussed.
Leukemia 1995 Sep
PMID:The IL-2 receptor complex: expression and function on normal and leukemic B cells. 765 7

The decrease in cell viability observed in vitro from the effect of chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxy-adenosine (CDA) on peripheral lymphocytes from 49 untreated CLL patients was investigated by the MTT colorimetric assay. The effects of recombinant-interleukin (r-IL)-2 and alpha-interferon (alpha-IFN) on drug-induced cell death were evaluated. r-IL-2 significantly increased in vitro resistance to CLB, while purine analog cytotoxicity was slightly reduced by the cytokine. The potential in vivo significance of r-IL-2, acting as a survival signal on CLB-induced cell death, is supported by the correlation between the lowest IL-2 serum levels, the highest in vitro sensitivity to CLB and a major clinical response after CLB treatment in six out of eight CLL patients. Using 25 samples, alpha-IFN enabled CLL cells to increase resistance to CLB, CDA and FAMP in 14, eight and seven samples, respectively; conversely, alpha-IFN showed a synergism with both CLB and FAMP in six samples and with CDA in four. These results correlate with immunoenzymatic assay data showing that alpha-IFN either up- or down-regulates tumor necrosis factor and IL-1 levels in supernatants of some CLL samples. Apparently, alpha-IFN plays a dual role in regulating drug-induced cell death, while IL-2 seems to solely favor cell survival in CLL.
Leukemia 1995 Sep
PMID:Modulation of purine analogs- and chlorambucil-induced cytotoxicity by alpha-interferon and interleukin-2 in chronic lymphocytic leukemia. 765 11

The M07e megakaryoblastic leukemia cell line is strictly dependent on either interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for continuous growth. This study shows that recombinant human stem-cell factor (rhSCF) can completely replace these lymphokines in supporting the continued propagation of M07e cells mostly by eliciting GM-CSF secretion in this target. In fact, in short-term proliferation assays the stimulatory activity of SCF is blocked about 75% by a GM-CSF-specific serum. In addition, we could detect GM-CSF expression by SCF-stimulated M07e cells, both at the protein and mRNA levels. In contrast, SCF does not induce transcripts for any other cytokine to which M07e cells are responsive, including IL-2, IL-3, IL-4, and IL-6. Overall, these data show that the ability of SCF to support the growth of this megakaryocytic cell line is mediated mostly by the induction of an autocrine loop of activation involving GM-CSF production. The finding that SCF can stimulate GM-CSF secretion also in an IL-2-dependent T-lymphoblastic leukemia cell line indicates that SCF can act on cells of both myeloid and lymphoid lineages, and that the ability to induce cytokines in target cells represents an important aspect of its mechanism of action.
Leukemia 1993 Feb
PMID:Human stem cell factor (c-kit ligand) induces an autocrine loop of growth in a GM-CSF-dependent megakaryocytic leukemia cell line. 767 80


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