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)

A new human monoclonal plasma cell line, designated UTMC-2, was established from the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related multiple myeloma. The cultured cells were Epstein-Barr virus-negative and exhibited the morphological and ultrastructural features characteristic of plasma cells. Immunohistochemical analyses revealed the presence of cytoplasmic IgA kappa as well as the plasma cell-associated surface antigens CD38 and CD56. Other B-cell markers, including CD10, CD19, CD20, and HLA-DR, were absent. The UTMC-2 cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA kappa synthesis and cell proliferation in a dose-dependent manner. In contrast, an IL-6 antisense oligonucleotide had an opposite effect. Although the UTMC-2 cells expressed IL-6 mRNA (as demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine in cell culture supernatants was less than that detectable by the enzyme-linked immunosorbent assay (ELISA) employed (i.e. <3 pg/ml). Further, cell growth was not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric analysis revealed that IL-6 receptors present on the surface of the UTMC-2 cells were not saturated with endogenous IL-6. Taken together, these results indicate that, in this human plasma cell line, IL-6 functions uniquely in an intracellular autocrine fashion to enhance Ig synthesis and cell growth. In this respect, the UTMC-2 cells represent a novel resource for further study of the role of IL-6 in the pathogenesis of multiple myeloma.
Leukemia 1994 Dec
PMID:Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line. 752 62

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

Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and plays an important role in megakaryocyte proliferation. The UT-7 cell line was established from a patient with megakaryoblastic leukemia, and its growth and survival are strictly dependent on interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), or IL-6. In this study, we showed that SCF also supported the growth of UT-7 in the absence of other cytokines and downregulated the cell surface c-kit receptors. Constitutive expression of SCF by introducing SCF expression vector made UT-7 grow factor-independently in liquid medium, but not in semisolid medium. This SCF-expressing factor-independent UT-7 (UT-7scf9) expressed the membrane bound form of SCF on their surface, but did not secrete detectable amounts of soluble SCF. UT-7scf9 formed aggregates as they grew in the absence of cytokines, and this aggregation was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF neutralizing antibody partially inhibited their growth. These results suggest that SCF stimulated UT-7 proliferation partially through the autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a membrane-bound form, which transduces its growth signal through c-kit receptor as they aggregate by cell-to-cell interaction.
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PMID:Cell-to-cell interaction of cytokine-dependent myeloblastic line constitutively expressing membrane-bound stem cell factor abrogates cytokine dependency partially through granulocyte-macrophage colony-stimulating factor production. 753 35

Factor-specific cell line bioassays were used to monitor the production in vitro by adult and fetal mouse organs of GM-CSF, G-CSF, M-CSF, Multi-CSF (IL-3), IL-6 and leukemia inhibitory factor (LIF). No tissue was observed to produce Multi-CSF. Highest producers of the other regulators were lung, muscle, thymus, heart and bone shaft and all tissues producing detectable growth factors produced all five with the same rank order of activity. Adult tissues produced more GM-CSF than G-CSF and less M-CSF than either, no differences being observed between male, female and pregnant female tissues. In contrast, the pregnant uterus produced high levels of M-CSF as did the fetal membranes and tissues with only low GM-CSF and no G-CSF production. Pre-irradiation did not alter the pattern of regulator production by adult tissues. The intravenous injection of endotoxin elevated serum levels of GM-CSF, G-CSF, M-CSF and IL-6 but the dominant rise was in G-CSF levels. The data indicating that multiple organs produce the regulators monitored in a common rank order suggest some overall linkage in their production with major differences between adult and fetal tissues.
Leukemia 1995 Sep
PMID:Production of hematopoietic regulatory factors in cultures of adult and fetal mouse organs: measurement by specific bioassays. 754 53

This study was aimed at evaluating the influence of 5637-conditioned medium (5637-CM) and human recombinant cytokines on both expression and function of P-glycoprotein (P-gp) in TF-1, a GM-CSF/IL-3-dependent acute myeloid leukemia cell line which constitutively expresses functional P-gp. P-gp expression was measured by flow cytometry using MRK16 monoclonal antibody. P-gp function was measured by rhodamine 123 (Rh 123) efflux kinetics. When TF-1 cells were cultured with 5637-CM (50% v/v), both P-gp expression and P-gp efflux capacity were increased in a time-dependent manner with a 4-fold increase in P-gp expression level at day 6 whereas TF-1 cell differentiation status remained unchanged as assessed by morphological studies, phenotypical and cytochemistry analysis. Recombinant cytokines including GM-CSF, G-CSF, IL-1 beta, IL-6, stem cell factor, LIF, erythropoietin, and IL-3 had no effect on P-gp expression whereas TNF alpha induced dose- and time-dependent P-gp and mdr-1 gene overexpression. However, TNF alpha-induced P-gp overexpression had no influence on P-gp efflux capacity. Furthermore, when TF-1 cells were exposed to IL-3 for periods longer than 1 month, we found that P-gp efflux capacity was increased as compared to cells cultured with GM-CSF whereas P-gp expression was unchanged. Both TNF alpha and IL-3 did not induce TF-1 differentiation. Collectively, these results suggest that cytokines may influence both expression and function of P-gp in TF-1 cells without interfering with their differentiation status. In contrast to cytokines, phorbol esters enhanced expression and efflux capacity of P-gp in parallel with TF-1 cell monocytic differentiation. Finally, our study suggests that paracrine and/or autocrine secretion of cytokines may interfere with P-gp activity in some acute myeloid leukemia cells.
Leukemia 1995 Oct
PMID:Effect of 5637-conditioned medium and recombinant cytokines on P-glycoprotein expression in a human GM-CSF-dependent leukemic myeloid cell line. 756 16

Polyomavirus was originally isolated by Ludwick Gross from a mixture that also contained a murine retrovirus. A possible pathogenic interaction between polyomavirus and an endogenous mouse retrovirus locus (mtv-7) in polyomavirus-induced cancer has also been reported. To study potential interactive effects of polyomavirus (Py) and Moloney murine leukemia retrovirus (M-MuLV), newborn Balb/c and NIH Swiss mice were infected with high titer wild-type Py (A2 strain) and M-MuLV. Dramatically stunted growth (runting) occurred in 100% of the doubly inoculated mice, while much lower frequency of runting occurred in animals infected with Py alone and not at all with M-MuLV-infected mice. In situ hybridization for Py DNA showed ongoing Py replication and inflammation in kidneys (atypical of most mice singly infected by Py) of runted doubly inoculated mice. In addition, high Py viral replication continued well past the usual acute stage termination. M-MuLV replication was also initially inhibited in bone marrow by simultaneous Py infection. No M-MuLV replication was seen in singly or doubly infected mouse kidneys. Runting was very rapid, observable within 2 days after co-infection, arguing against an adaptive or antigen-specific immunological mechanism. One possibility was that a cytokine-driven acute response mechanism was involved. Supporting this view, RNAse protection assays for various cytokine RNAs showed that several were specifically elevated in kidneys of doubly infected mice. Three patterns were observed: (1) IL-6 was elevated in doubly infected mice early after infection (7 days), but it declined at later times (19 days); (2) IFN-gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3) TNF-alpha, IL-12p40, and possibly TNF-beta were elevated only at late times. While the cytokines in the third category might be indicative of infiltrating inflammatory cells, it seems possible that cytokines in the first or second categories might be involved in establishing runting and ongoing polyoma DNA replication in the doubly infected mice.
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PMID:A model for mixed virus disease: co-infection with Moloney murine leukemia virus potentiates runting induced by polyomavirus (A2 strain) in Balb/c and NIH Swiss mice. 757 5

Expansion of the natural killer (NK) subset of lymphocytes represents a rare leukemia phenotype with variations in clinical presentation, morphology, surface phenotype, and effector function. This paper reports on a 5-year-old male patient who had an unusual presentation of an NK cell leukemia that was initially diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of undifferentiated cells with the following phenotype: CD56bright+, CD33dim+, CD45-, CD2-, CD19-, CD16-, and CD57-. Cytochemistry was noncontributory. The patient, having failed to respond to conventional neuroblastoma chemotherapy, was subsequently diagnosed as having NK cell leukemia based on functional in vitro assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy but relapsed 4 weeks into treatment and eventually died 25 weeks after initial presentation. The cell surface phenotype observed is consistent with a rare NK cell subset, the biology of which has not been well defined. Freshly isolated BM cells killed K562 cells in a conventional 51Cr-release assay. Both interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) induced LAK activity against the Daudi cell line. IL-2 induced proliferation of the leukemic cells. TNF-alpha, IFN-gamma, IL-6, IL-1ra, and TGF-beta levels were assessed and found to be concentrated in BM, in contrast to plasma samples. TNF-alpha was present at a high concentration in BM (150.9 pg/ml), probably a reflection of the associated disease pathology of severe bone pain and pyrexia. In summary, this paper details clinical and laboratory investigations of a leukemia of a rare NK cell subset.
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PMID:Recognition of unusual presentation of natural killer cell leukemia. 757 92

Mutagenesis of a region of human interleukin (IL)-6 which is important for triggering signal transduction via the IL-6 receptor beta-chain (gp130) has lead to the isolation of a variant of human IL-6 (IL-6.Q160E/T163P), which could antagonize the biological activity of wild type IL-6 on the human EBV transformed B cell line CESS and the human hepatoma cell line HepG2. Surprisingly this antagonistic IL-6 variant had an agonistic effect on the human myeloma cell line XG-1, albeit at a 1000-fold higher concentration than wild type IL-6. This residual activity of the mutant arose from triggering gp130, because it could be inhibited by a gp130 specific mAb. Extensive mutagenesis of residues between Q153 and H165 of human IL-6, a region which is partly homologous in cytokines which also signal via gp130 (oncostatin M, ciliary neurotrophic factor, leukaemia inhibitory factor, IL-11), did result in the isolation of a second antagonist for IL-6 activity on CESS and HepG2 cells. However on XG-1 cells this variant was active as well. These results suggest that (an) additional region(s) of the IL-6 molecule might be involved in gp130 triggering. Recently we indeed found that residues Lys42-Ala57 are also important for gp130 triggering. Inhibition experiments with neutralizing IL-6R alpha-chain specific mAb show that this region can be functionally separated from the Q153-H165 region. These findings have important implications for the development of receptor antagonists of IL-6 and IL-6 family members.
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PMID:Functional distinction of two regions of human interleukin 6 important for signal transduction via gp130. 757 77

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


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