Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CMK cell line is an acute megakaryoblastic leukemia cell line established from a patient with Down's syndrome, and is known to possess characteristics of normal megakaryocytes. Several cytokines with the ability to stimulate megakaryopoiesis, such as interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulated colony formation by CMK cells. The present study revealed that tumor necrosis factor-alpha (TNF-alpha) stimulated colony formation by CMK cells; the potency was almost equal to that of IL-3, IL-6 or GM-CSF. Scatchard plot analysis revealed that CMK cells possess two types of specific binding sites for TNF-alpha. The high-affinity binding sites had an affinity constant of 0.18 nM, and numbered 5,000. The low-affinity binding sites had an affinity constant of 1.8 nM and numbered 19,000. These results raise the possibility that TNF-alpha can act as a growth-stimulating agent on megakaryocyte-lineage cell line.
 ...
PMID:Tumor necrosis factor-alpha stimulates colony formation by a megakaryoblastic leukemia cell line, CMK. 142 11

We have recently reported that normal long-term marrow cultures (LTMC) treated with recombinant human macrophage colony-stimulating factor (rhCSF-1), as well as LTMC from patients with acute myelogenous leukemia (AML), produce a soluble activity capable of inhibiting hemopoietic colony formation in semisolid cultures. In the present study, we have found that such an activity is produced, both in normal and AML LTMC, by an adherent, nonfibroblastic cell population (most likely macrophages), and also by blast cells developed in AML LTMC. The presence of the inhibitory activity correlated with increased levels of tumor necrosis factor (TNF) in the culture supernatants. Part of the activity (30%) produced in rhCSF-1-treated normal LTMC was neutralized in colony assays by anti-TNF alpha monoclonal antibody. In contrast, the soluble inhibitory activity from AML LTMC was completely neutralized by anti-TNF alpha. However, addition of anti-TNF alpha (every 72 h, from day 0 to 21, at 125 ng/ml) to AML LTMC resulted in only partial neutralization of the inhibitory activity, indicating that production of TNF alpha is just one of the mechanisms by which normal hemopoiesis is inhibited in AML LTMC, and that other factors are involved in this process. In keeping with this idea, we found very high levels of prostaglandin E, a hemopoietic inhibitor, in the supernatant of cultures that contained the soluble inhibitory activity. Interestingly, rhCSF-1 showed opposite effects on TNF production in normal (up-regulation) and AML (down-regulation) LTMC, which suggests the presence of functionally abnormal, leukemia-derived macrophages in AML LTMC.
Leukemia 1992 Nov
PMID:Production of tumor necrosis factor-alpha in human long-term marrow cultures from normal subjects and patients with acute myelogenous leukemia: effect of recombinant macrophage colony-stimulating factor. 143 97

Since autocrine stimulation by tumor necrosis factor-alpha (TNF alpha) may be implicated in the proliferation of normal and malignant B cells, we measured the production of TNF alpha protein by these cells in response to various B-cell stimulatory agents. Purified malignant and non-malignant B lymphocytes were incubated with interleukin-4 (IL4), interferon-alpha (IFN alpha) and IFN gamma, and the supernatants were tested for the production of TNF alpha using an enzyme-linked immunosorbent assay (ELISA). Chronic lymphocytic (CLL) and prolymphocytic (PLL) leukemia cells produced low amounts of TNF alpha, irrespectively of the addition of inducers. Normal B lymphocytes (tonsillar and blood) produced TNF alpha, but the level was not influenced by any of the inducers tested. Hairy cell leukemia (HCL) cells produced TNF alpha in the absence of stimuli and this production was markedly enhanced by addition of IFN alpha or, to a lesser extent, by IFN gamma and IL4. These results contradict the hypothesis that IFN alpha exerts its therapeutic action in HCL by inhibition of autocrine TNF alpha production.
Leukemia 1992 Feb
PMID:Production of tumor necrosis factor-alpha by normal and malignant B lymphocytes in response to interferon-alpha, interferon-gamma and interleukin-4. 842 86

Adoptive immunotherapy with interleukin 2-induced lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL) and the induction of anti-tumor responses by IL-2 alone having proven to be promising approaches in cancer therapy. The present study investigated the cytotoxicity of LAK cells towards human leukemia cells. LAK cells were generated by culturing peripheral blood mononuclear cells from normal donors for six days in the presence of recombinant interleukin 2 (IL-2). Cytotoxicity was evaluated using a standard 4-h chromium-release assay. A significant lysis of fresh uncultured leukemia cells by IL-2-activated killer cells could be detected in 77 of 150 leukemias examined. The mean Cr-release was 35.7 +/- 12.9% in the LAK cell-sensitive vs 9.9 +/- 5.9% in the resistant leukemias. With a view to the therapeutic utilization of the LAK-cell system, we attempted to improve the efficiency of its cytotoxic mechanisms. Combined application of IL-2 and interferon-alpha, interferon-gamma, or tumor necrosis factor-alpha in cultures for generation of activated killer cells significantly improved the effectiveness of cytotoxic mechanisms. Our results suggest that the performance of adoptive immunotherapy with ex vivo-activated LAK cells and the in vivo induction of cytotoxic immune responses by IL-2 alone or combined with different lymphokines or cytokines may be of value in treating human leukemia, especially when the tumor burden is low, e.g. during maintenance therapy or after bone marrow transplantation to eliminate minimal residual disease or in early relapse.
 ...
PMID:Cytotoxicity of interleukin 2-induced lymphokine-activated killer (LAK) cells against human leukemia and augmentation of killing by interferons and tumor necrosis factor. 156 Jun 76

The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines.
Leukemia 1992
PMID:Growth restraint and differentiation by LPS/TNF-alpha/IFN-gamma reorganization of the microtubule network in human leukemia cell lines. 160 11

Soluble suppressor factor (SSF), first described in association with HIV-1 infection in vivo, is a molecule(s) capable of inhibiting T cell-dependent immune reactivity. Its relationship to human immunodeficiency virus (HIV) was further defined as supernatants of mononuclear cell cultures from HIV-1-seropositive carriers, CD4+ T lymphocytes infected with HIV-1 in vitro, and a T cell hybridoma incorporating CD4+ lymphocytes from an HIV-1-seropositive individual were shown to elaborate factors with similar activity profiles. These factors were recognized antigenically by certain antibodies directed against epitopes of p15E, a transmembrane protein of murine leukemia virus which shares regions of identity with proteins deduced from human endogenous retroviral envelope transcripts as well as HIV. These reagents precipitated a single-chain, nonglycosylated, nonviral protein of molecular weight 57,000 Da from SSF-producing cells. There was no cross-reactivity with antisera recognizing the IL-2R alpha-chain (CD25) or tumor necrosis factor. This molecule was present in very low levels in PHA-activated T lymphocytes and was upregulated following their infection with HIV-1. Isolation of HIV-linked SSF should permit comparisons with other virion, cellular, and serum inhibitory substances described in AIDS, and perhaps suggest therapeutic strategies.
 ...
PMID:A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E. 169 8

Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.
Leukemia 1990 Aug
PMID:Long-term effects of 2'-deoxycoformycin treatment on cytokine production in patients with hairy cell leukemia. 169 12

Mast cells and basophils have been known to play a central role in allergic inflammation through the release of chemical mediators by cross-linkage of IgE receptors. The IgE receptor triggering and calcium ionophore A23187 have also been shown to induce gene expression and production of tumor necrosis factor (TNF) by rat basophilic leukemia cells. In the present study, we examined whether IgE receptor triggering could induce gene expression and production of TNF in rat lung tissue. The lung tissue released not only histamine but also cytotoxic activity on L929 cells 2 and 4 h after incubation with dinitrophenyl conjugated to ovalbumin (DNP-OVA) following passive sensitization with anti-DNP monoclonal rat IgE antibody, whereas neither DNP-OVA nor anti-DNP IgE antibody could induce the cytotoxic activity when used solely. Calcium ionophore A23187 also could induce both histamine release and cytotoxic activity. These activities induced by IgE receptor triggering, A23187, and lipopolysaccharide were completely neutralized by preincubation with anti-mouse TNF-rabbit serum, but not with normal rabbit serum. Northern blot analysis using cDNA probe of mouse TNF demonstrated expression of TNF gene as early as 2 h after IgE receptor triggering. These data demonstrating that IgE receptor triggering induced gene expression and production of TNF in lung tissue suggest the participation of TNF in the pathogenesis of late asthmatic response through its biologic activities such as the attraction and activation of neutrophils and eosinophils.
 ...
PMID:Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue. 169 98

The disappearance of normal hematopoiesis during acute nonlymphoblastic leukemia (ANLL) is poorly understood. Several reports indicate that conditioned medium obtained from leukemic cells might inhibit the formation of normal hematopoietic progenitors. However, these blast-conditioned medium (BCM) inhibitory activities are not well characterized. In order to evaluate whether BCM might contain an activity inhibiting the growth of normal marrow progenitors, BCM from 13 consecutive patients with ANLL were tested on normal bone marrow in methylcellulose assays. In all the cases, a significant inhibition of the growth of granulocyte-macrophage colony-forming unit (CFU-GM) progenitors was observed, whereas erythroid burst-forming unit (BFU-E) progenitors were not affected. Further characterization of the BCM inhibitory activity showed using both a biological assay and RIA, the presence of tumor necrosis factor-alpha (TNF-alpha) in 10 out of 13 BCM. Northern blot analysis performed in six patients showed a correlation between the expression of TNF-alpha mRNA by leukemic cells and the presence of TNF-alpha in BCM. Moreover, the BCM inhibitory activity could be neutralized with an anti-TNF-alpha antiserum. These data indicate that leukemic cells express and release frequently TNF-alpha, which may therefore play an important role in the inhibition of granulopoiesis during leukemia.
 ...
PMID:Secretion of tumor necrosis factor-alpha by fresh human acute nonlymphoblastic leukemic cells: role in the disappearance of normal CFU-GM progenitors. 169 75

We have previously shown that maturing neoplastic cells from patients with stable phase chronic myelogenous leukemia (SP CML) constitutively produce granulocyte colony-stimulating factor (G-CSF) and are also receptive for this molecule. G-CSF functions as an endogenous growth factor in SP CML, and thus is responsible for divisions in maturing leukemic cells leading to an expansion of the compartment of mature cells. In the investigations to be reported below, the effects of various hematopoietic inhibitor molecules on the expression of the G-CSF gene by SP CML bone marrow cells enriched for promyelocytes/myelocytes were examined at the mRNA and protein level. We show that exposure of SP CML bone marrow promyelocytes/myelocytes to recombinant human (rh) interferon (IFN)-gamma but not to rh IFN-alpha, rh tumor necrosis factor (TNF)-alpha, and rh lymphotoxin (LT) leads to downregulation of G-CSF expression and interruption of the G-CSF-mediated endogenous growth stimulation. The action of G-CSF takes place at the posttranscriptional level and involves an acceleration of decay of steady-state levels of G-CSF transcripts in the malignant cell population.
Leukemia 1990 Nov
PMID:Gamma-interferon interrupts growth stimulation in chronic myelogenous leukemia established by endogenous granulocyte colony-stimulating factor. 170 Feb 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>