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)

Spontaneous secretion of interleukin 1 (IL-1) alpha, IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) from acute myelogenous leukaemia (AML) blasts showed significant correlation, and detectable levels of all cytokines were seen for a majority of patients. IL-3 and granulocyte/macrophage colony-stimulating factor increased secretion of IL-1 alpha, IL-1 beta and TNF-alpha for a majority of AML patients, whereas IL-4 decreased cytokine secretion. The effect of IL-6 and stem cell factor on cytokine secretion varied between different patients. A wide variation in IL-1 alpha, IL-1 beta and TNF-alpha secretion between different patients was seen both for spontaneous secretion and in the presence of all cytokines.
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PMID:Cytokine modulation of interleukin 1 and tumour necrosis factor-alpha secretion from acute myelogenous leukaemia blast cells in vitro. 753 Jul 89

We have investigated the effects of interleukin-4 (IL-4) on the proliferation of chronic myelomonocytic leukemia (CMMoL) cells in the chronic and leukemic transformation phases in vitro. CMMoL cells formed colonies spontaneously in both phases. IL-4 suppressed the spontaneous growth in the chronic phase, but on the other hand, stimulated colony formation in the leukemic transformation phase. Anti-IL-6 antibody inhibited spontaneous colony formation in both phases. CMMoL cells in both phases produced high levels of IL-6, compared with those produced by acute myelogenous leukemia (AML) cells showing myelomonocytic differentiation and normal monocytes. IL-4 suppressed the IL-6 production by CMMoL cells in both phases. None of anti-IL-6, anti-macrophage colony-stimulating factor (M-CSF), anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-tumor necrosis factor-alpha (TNF-alpha) and anti-IL-1-beta antibodies inhibited IL-4-stimulated colony formation. These results suggest that IL-4 directly stimulates the growth of CMMoL cells once leukemic transformation has occurred and that the therapeutic use of IL-4 for CMMoL should be viewed with caution, especially in the leukemic transformation phase.
Leukemia 1995 Jun
PMID:IL-4 stimulates the growth of chronic myelomonocytic leukemia cells (CMMoL) once leukemic transformation has occurred. 759 69

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

The clinical use of cytokines is still expanding as the knowledge of beneficial effects as adjunct to cancer treatment is increasing. G-CSF and GM-CSF stimulates hemopoietic recovery after myelosuppressive chemotherapy and enhances engraftment after bone marrow transplantation. New cytokines as IL-1, IL-3, IL-4 and IL-6, are studied in clinical trials and combinations of these with stem cell factor seem promising in ex vivo expansion of stem cells. GM-CSF also have antitumor effects. The most recently discovered hemopoietic growth factor is thrombopoietin, from which probably especially patients with leukemia will benefit.
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PMID:Hemopoietic growth and inhibitory factors in treatment of malignancies. A review. 760 52

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

We studied the adhesion properties of peripheral blood leukemic cells from 10 patients with adult T-cell leukemia (ATL) to endothelial cells to better understand the mechanism of leukemic cell infiltration. ATL cells expressed lymphocyte function-associated antigen-1 (LFA-1), but the expression of very late antigen-4 (VLA-4) and sialyl-Lewisx (SLex) was variable. They did not express sialyl-Lewisa (SLea). Cell adhesion assays, which were performed in nine patients, showed marked adhesion of ATL cells to interleukin [IL]-1-activated human umbilical vein endothelial cells (HUVEC). A monoclonal antibody (MoAb) against E-selectin consistently inhibited ATL cell adhesion, and an MoAb against vascular cell adhesion molecule-1 (VCAM-1) or an MoAb against VLA-4 sometimes diminished it. In contrast, an MoAb against LFA-1 had a minor effect on freshly isolated ATL cell adhesion to HUVEC. The percentage of SLex+ cells in the cell population adherent to IL-1-activated HUVEC was slightly higher than that in unseparated cells. These results, together with the detection of E-selectin expression on the endothelium at ATL skin lesions, indicate that E-selectin-mediated adhesion is the major pathway for the adherence of ATL cells to endothelial cells. In addition, the ligand for E-selectin on ATL cells appears to differ from that on neutrophils.
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PMID:E-selectin and vascular cell adhesion molecule-1 mediate adult T-cell leukemia cell adhesion to endothelial cells. 768 74

We investigated hematopoietic growth factor (HGF) and cytokine gene expression in the bone marrow (BM) and peripheral blood (PB) of healthy individuals as a starting point for delineating the physiologic role of cytokines in steady state hematopoiesis. BM biopsy specimens and PB samples from 7 healthy individuals were analyzed by polymerase chain reaction amplification of reverse-transcribed RNA using gene-specific primer sets. Consistent gene expression in the BM of all 7 individuals was detected for macrophage colony-stimulating factor (CSF), stem cell factor, interleukin-6 (IL-6), IL-7, erythroid-potentiating factor, erythroid-differentiating factor, and insulinlike growth factor 1, all cytokines with reported direct stimulatory effects on in vitro hematopoiesis. Of these, erythroid-potentiating factor and erythroid-differentiating factor appeared to be the only stimulating factors that were also expressed in the PB. Among the cytokines with inhibitory effects on in vitro hematopoiesis IL-4, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, transforming growth factor-beta, and macrophage inflammatory protein-1 alpha were expressed in the BM of the 7 individuals. Except for TNF-alpha, the latter cytokines were also expressed in the PB. Consistent expression in the BM and PB of all tested individuals was also observed for IL-1 beta, IL-1 receptor antagonist, and IL-1 beta converting enzyme, which are all members of the IL-1 family with a possible indirect effect on hematopoiesis. Remarkably, no expression of granulocyte CSF, granulocyte-macrophage CSF, and IL-3 was found in the BM or PB of all investigated individuals (n = 15). This was also the case for IL-1 alpha, IL-2, IL-5, IL-9, IL-12, IL-13, leukemia-inhibiting factor, interferon-gamma, and inhibin. Weak IL-8 and IL-10 expression was found in the BM and/or PB of a minority of investigated individuals. These findings provide insight into which cytokines or HGFs potentially are involved in the autocrine or paracrine regulation of in vivo steady state hematopoiesis. The absence of expression of granulocyte CSF, granulocyte-macrophage CSF, and IL-3 in the BM of healthy individuals implicates that it is highly unlikely that these HGFs are involved in the autocrine or paracrine regulation of constitutive hematopoiesis.
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PMID:Constitutive in vivo cytokine and hematopoietic growth factor gene expression in the bone marrow and peripheral blood of healthy individuals. 771 76

Murine embryonic stem cells are able to differentiate into embryoid bodies (EBs) in vitro in the absence of leukemia-inhibitory factor with the formation of different types of hematopoietic precursors within these EBs. With the aim of determining the in vitro requirements for the continued development of hematopoietic colony-forming cells (CFCs) and their progeny from embryonic stem-derived cells, cells from EBs disrupted after 9 days of formation in the absence of leukemia-inhibitor factor were cultured under different conditions. Low numbers of day-9 EB cells (5 x 10(5) or less) cultured in the presence of several growth factors (interleukin-3 [IL-3], IL-1, c-kit ligand, basic fibroblast growth factor, insulin growth factor-1, IL-6, granulocyte colony-stimulating factor, fetal liver kinase-2 ligand) develop few or no CFCs after 1 week of culture. When these cells are plated on irradiated NIH-3T3 with IL-3 or c-kit ligand or combinations containing these and other growth factors, they are able to generate CFCs for at least 3 weeks. These cultures were found to include granulocytic, monocytic, erythrocytic, and megakaryocytic cells. Transwell cultures in which NIH-3T3 cells were separated from the EB cells and cultures in which cells were replaced by NIH-3T3 conditioned medium showed that the interaction between EB-derived cells and NIH-3T3 is via a soluble factor(s). These studies show that maximal generation of hematopoietic CFCs from precursors present in day-9 EBs is stimulated by a combination of known hematopoietic growth factors and a soluble factor(s) produced by NIH-3T3 cells.
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PMID:Generation of hematopoietic colony-forming cells from embryonic stem cells: synergy between a soluble factor from NIH-3T3 cells and hematopoietic growth factors. 775 44

Cord blood has been used successfully for stem cell transplantation in several haematological conditions: Fanconi's anaemia, leukaemia and Wiskott-Aldrich syndrome. On account of the low incidence of GVHD observed following cord blood transplantation, it has been suggested that cord blood be used for HLA-matched, or perhaps one or two antigens mismatched, and unrelated stem cell transplantation. Based on an extensive immunophenotype-functional correlation, we determined that cord blood contains mainly immature unprimed T lymphocytes that are predominantly suppressor cells. Recent findings suggest that dysregulated production of cytokines (IL-1, IL-2, TNF alpha) plays a role in GVHD. We showed that T cells in cord blood express receptors for IL-2, TNF alpha, but no receptors for IL-1. Similarly, NK cells, one of the effector cells of GVHD, express receptors for TNF alpha and gamma IFN but do not express receptors for IL-1, nor IL-2R alpha-chain (CD25) although IL-2R beta-chain is expressed. The potential for activation of T lymphocytes and NK cells therefore exists in the context of bone marrow transplantation. However, the high number of suppressor cells in cord blood most likely modulate the activation of lymphocytes and NK cells thereby minimizing GVHD.
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PMID:Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation. 777 9

Leukaemia Inhibitory Factor (LIF) has been implicated in connective tissue damage in arthritis. We have previously shown that LIF stimulates proteoglycan release in pig cartilage explants. The aim of this study was to determine whether LIF modulates proteoglycan synthesis in vitro. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagles medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative control) or LIF. During the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose-dependent suppression of proteoglycan synthesis was observed with murine and human recombinant LIF in pig and goat cartilage. The degree of inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inhibitor of proteoglycan synthesis in cultured pig and goat articular cartilage.
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PMID:Leukaemia inhibitory factor (LIF) suppresses proteoglycan synthesis in porcine and caprine cartilage explants. 778 32


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