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)

Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.
Leukemia 1992 Dec
PMID:Measurement of serum cytokine levels in patients with myelodysplastic syndromes. 128 Jul 51

Recombinant human tumor necrosis factor-alpha (TNF-alpha) was found to stimulate the growth of CMK, a human megakaryoblastic leukemia cell line. This stimulatory effect of TNF-alpha was blocked by anti-TNF-alpha antibody, but antibodies to recombinant human interleukin 3, granulocyte-macrophage colony-stimulating factor and interleukin 6 (all growth factors for CMK cells) did not reduce the stimulatory effect of TNF-alpha. Scatchard analysis showed that CMK cells expressed TNF-alpha receptors on the cell surface. The growth of CMK cells was also stimulated by lymphotoxin, which shares the same receptor as TNF-alpha. These results suggest that TNF-alpha stimulated the growth of CMK cells directly via its specific receptor.
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PMID:Stimulatory effect of tumor necrosis factor-alpha on the growth of CMK, a human megakaryoblastic leukemia cell line. 131 36

The pathogenesis of retrovirus-induced erythroid aplasia in cats is unknown. In studies to define mechanisms of cytotoxicity associated with retroviral infections, bone marrow mononuclear cells (BMMC) from healthy specific pathogen-free cats were co-cultured with uninfected feline embryonic fibroblasts (FEA cells) and FEA cells infected with feline leukemia virus (FeLV) of subgroup A (FEA-A) or subgroup C (FEA-C). Moderate to marked cytotoxicity (CPE) developed in co-cultures of BMMC and FEA-C cells on Days 5 to 7 of incubation but not in co-cultures of BMMC and FEA-A or BMMC and uninfected cells (FEA-CT). Cytotoxicity was associated with adherent cells of light density (1.056) from bone marrow and peripheral blood, which were positive for alpha naphthyl butyrate esterase activity. Stimulation of adherent cells with phorbol ester or addition of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) caused similar CPE in FEA-CT cells. The TNF-alpha concentrations in the culture supernatants of BMMC+FEA-C were higher than those of BMMC+FEA-A or BMMC+FEA-CT, and addition of anti-TNF antibodies to the cultures blocked the CPE. These data support the hypothesis that macrophages exposed to FeLV-C cause CPE in co-cultures of BMMC and FEA cells by a mechanism involving TNF-alpha. It is suggested that TNF-alpha may be involved in the suppression of hematopoiesis in cats which develop FeLV-C induced erythroid aplasia.
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PMID:Cytotoxicity in feline leukemia virus subgroup-C infected fibroblasts is mediated by adherent bone marrow mononuclear cells. 131 51

The effects of tumor necrosis factor-alpha (TNF-alpha) on feline bone marrow hematopoietic progenitors were evaluated by exposing bone marrow mononuclear cells from specific pathogen-free cats to different concentrations of TNF-alpha (ranging from 50 to 800 pg/ml) for 2 h before plating for clonal assays of colony-forming units. TNF-alpha caused a dose-dependent suppression of feline erythroid colony-forming units (CFU-E) and erythroid burst-forming units (BFU-E), whereas granulocyte-macrophage colony-forming units (CFU-GM) were minimally affected. TNF-alpha concentrations as low as 200 pg/ml significantly inhibited growth of erythroid progenitors. Addition of polyclonal rabbit anti-TNF-alpha antibodies completely neutralized the suppressive effect of TNF-alpha on erythroid progenitors. At higher concentrations of TNF-alpha (800 pg/ml), 35% of CFU-E and 21% of BFU-E still survived, indicating that some erythroid progenitors are not sensitive to a single exposure of TNF-alpha in vitro. These results suggest that TNF-alpha may play a role in regulating hematopoiesis in cats and may be involved in the pathogenesis of erythroid aplasia in cats infected with feline leukemia virus.
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PMID:Effects of tumor necrosis factor-alpha on normal feline hematopoietic progenitor cells. 132 Oct 52

Interleukin-2 (IL-2) promotes the generation and proliferation of killer cells in the peripheral blood and bone marrow (BM) both in vitro and in vivo. When employed in a syngeneic bone marrow transplantation (BMT) setting and followed by IL-2 therapy, murine BM cells activated with IL-2 in vitro (ABM) demonstrate potent graft-versus-leukemia (GVL) and anticytomegalovirus effects. ABM cells retain the capacity to reconstitute the hemopoietic system both in normal and leukemic mice. This therapy does not cause graft-versus-host disease (GVHD). Human ABM cells carry out purging of leukemia without loss of progenitor cell activity in vitro. The purging ability of ABM can be augmented by interleukin-1, interferon, and tumor necrosis factor. IL-2 therapy stimulates the veto suppressor cell activity of T cell-depleted BM, and has reduced GVHD and permitted engraftment of mismatched allogeneic BM in murine models. Future studies should determine the optimum treatment schedules with IL-2 for improving the GVL effect in autologous BMT, and for abolishing GVHD in allogeneic BMT settings.
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PMID:Interleukin-2 in bone marrow transplantation: preclinical studies. 132 64

An 85-kDa protein was identified in adriamycin-resistant tumor cells recognized by monoclonal antibody MRK-20. Recently, the monoclonal antibody MRK-20 was found to be reactive to human peripheral mononuclear cells. In order to investigate the molecular function of the 85-kDa protein, we carried out flow cytometric analysis of the expression of the 85-kDa protein during monocytic differentiation of the hematopoietic cells. Human myelomonocytic leukemia THP-1 cells were induced to differentiate into macrophage-like cells by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). A maximum of 55% of the cells expressed the 85-kDa protein along with the CD-14 antigen, which is a surface marker of monocytes and macrophages. The kinetic analysis revealed that the 85-kDa protein appeared prior to the expression of the CD-14 antigen. The 85-kDa protein was also coexpressed with CD-14 in THP-1 cells that were induced to differentiate by recombinant tumor necrosis factor-alpha, which is one of the physiological inducers of monocytic differentiation. In human erythroleukemia, HEL cells, the 85-kDa protein was constitutively coexpressed with CD-14. The expression of both the 85-kDa protein and CD-14 was drastically reduced during the megakaryocytic differentiation of the HEL cells with TPA. These results suggest that the 85-kDa protein could be expressed on monocytic cells as well as CD-14 and that the expression of the 85-kDa protein might be regulated at an earlier stage of monocytic differentiation of hematopoietic cells than the expression of CD-14.
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PMID:Expression of 85-kDa protein of adriamycin-resistant tumor cells during hematopoietic differentiation of THP-1 and HEL cells. 137 89

The c-kit proto-oncogene encodes a transmembrane glycoprotein identical to the receptor for the recently cloned stem cell factor (SCF). The present study examines constitutive synthesis of transcripts in primary acute myelogenous leukemia (AML) blasts and the effects of recombinant human tumor necrosis factor (TNF)-alpha on c-kit mRNA expression in these cells. The c-kit transcripts were detectable at low levels in 10 of 10 different AML samples investigated. TNF treatment of AML cells was associated with enhanced c-kit mRNA expression in all specimens. Nuclear run-on transcription assays indicated that the c-kit gene was transcriptionally active in all leukemias examined and the rate of transcription was unaffected by exposure to TNF, suggesting posttranscriptional control mechanisms of c-kit mRNA accumulation. In the absence of TNF, the half-life of c-kit transcripts was 2 to 3 hours, while in TNF-treated AML cells, c-kit half-life was found to be 5 to 9 hours. Inhibition of protein synthesis reduced TNF-induced c-kit mRNA expression by Northern blot analysis, but did not affect the rate of c-kit gene transcription. In the presence of inhibition of protein synthesis, the half-life of c-kit transcripts in TNF-induced leukemia cells decreased to 2 to 4 hours. These findings indicate that levels of c-kit mRNA are controlled by a labile protein that is involved in TNF-mediated stabilization of c-kit transcripts. The effects of TNF-alpha also extended to the protein level in that TNF-alpha treatment of primary AMLs was associated with enhanced surface expression of the SCF receptor by some of these cells. While exogenous SCF induced clonogenic growth of all primary AML samples investigated, TNF-alpha failed to stimulate leukemic cells to proliferate. However, the combination of SCF and TNF-alpha resulted in synergistic growth stimulation in seven of nine different AML specimens investigated. The finding of transmodulation of the SCF receptor through posttranscriptional modifications might further contribute to our understanding of the synergistic interplay of TNF-alpha and SCF.
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PMID:Functional expression of c-kit by acute myelogenous leukemia blasts is enhanced by tumor necrosis factor-alpha through posttranscriptional mRNA stabilization by a labile protein. 1101 49

Oxygen radical scavengers, such as dithiocarbamates and cysteine derivatives, inhibit activation of the ubiquitous transcription factor nuclear factor kappa B (NF-kappa B) after treatment of cells with tumor necrosis factor, phorbol ester, and interleukin-1. An involvement of oxygen radicals was more directly evident from the induction of NF-kappa B by low concentrations of H2O2 and the demonstration that cells stimulated with various NF-kappa B inducers release H2O2 and superoxide. In this study, we used the antioxidant pyrrolidine dithiocarbamate (PDTC) to investigate whether the activation of NF-kappa B by the viral transactivator Tax from human T-cell leukemia virus type I also depends on the production of reactive oxygen intermediates. The Tax-induced activation of the DNA-binding activity of NF-kappa B in Jurkat T cells was potently suppressed by micromolar concentrations of PDTC. Within the same concentration range, PDTC and two other dithiocarbamates also strongly interfered with transactivation of the long terminal repeat (LTR) of human immunodeficiency virus type 1 by Tax but had no effect on transactivation of the same LTR by Tat. Transactivation of the human T-cell leukemia virus type I LTR by Tax was also barely influenced. Tax seems to activate NF-kappa B by a mechanism shared with all other inducers of NF-kappa B tested so far. It appears that one of the pleiotropic activities of Tax leads to an enhanced production of oxygen radicals that are required for activation of NF-kappa B.
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PMID:Antioxidants selectively suppress activation of NF-kappa B by human T-cell leukemia virus type I Tax protein. 140 92

The effects of interleukin-1 beta (IL-1) and IL-4 were studied on the proliferation of acute myeloid leukemia (AML) cells. IL-1 stimulated tritiated thymidine (3H-TdR) uptake of AML cells in 8/12 cases, whereas IL-4 enhanced 3H-TdR uptake in 5/12. Combination of both factors resulted in an additive effect in 6/12 cases which could be abrogated by the addition of anti-granulocyte-macrophage colony stimulating factor (GM-CSF). To study whether IL-1, IL-4, or IL-1 plus IL-4 affects the AML progenitor cell directly or indirectly by the release of endogenous factors, supernatants of stimulated AML cells (n = 6) were analyzed for GM-CSF, IL-6, and tumor necrosis factor-alpha (TNF) production. IL-1 induced the endogenous secretion of GM-CSF, IL-6, and TNF in most cases. In contrast, no secretion of growth factors was induced by IL-4, whereas in 2 cases IL-4 suppressed the IL-1-induced secretion of GM-CSF, TNF, and IL-6. This was associated with a decline in the proliferative response to IL-1 measured in a clonogenic assay. In addition it was shown that exogenous supplied GM-CSF and TNF could raise the suppressive effects of IL-4 on the IL-1-supported proliferation. In summary these data indicate that the IL-4-supported proliferation is not caused by the endogenous secretion of GM-CSF, IL-6, and TNF. Furthermore the suppressive effect of IL-4 on the IL-1-induced proliferation in some cases may be caused by a reduced secretion of GM-CSF, TNF, and IL-6.
Leukemia 1992 Oct
PMID:The effects of IL-1 beta and IL-4 on the proliferation and endogenous secretion of growth factors by acute myeloblastic leukemic cells. 140 54

The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. 141 3


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