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)

Oncostatin M (OSM) is a 28-kDa glycoprotein produced by stimulated macrophages and T lymphocytes that inhibits the proliferation of a number of different cell lines derived from solid tumors. Analysis of both amino acid sequence and gene structure has demonstrated that OSM is a member of a cytokine family that includes leukemia inhibitory factor (LIF), IL-6, and granulocyte colony-stimulating factor (G-CSF). We demonstrate that, like LIF, IL-6 and G-CSF, OSM can induce the differentiation of the myeloblastic M1 murine leukemia cells into macrophage-like cells. The morphologic and functional changes induced by OSM are more similar to those observed with LIF and IL-6 than those induced with G-CSF. OSM can also induce the differentiation of the histiocytic U937 human leukemia cells in the presence of granulocyte-macrophage CSF, a property shared with LIF and IL-6. In murine M1 cells, binding of labeled OSM is completely inhibited by excess LIF or OSM, reflecting the binding of OSM to the high affinity form of the murine LIF receptor. In contrast, the binding of labeled OSM to human U937 leukemia cells is inhibited by OSM, but the inhibition by LIF is significantly less. These results suggest that, in human leukemia cells, OSM may act through the LIF receptor and an OSM-specific receptor. The existence of an OSM-specific receptor was confirmed by both growth inhibition and competition binding assays on A375 human melanoma cells. The growth of human A375 cells was inhibited by OSM and IL-6 but not LIF or G-CSF. Neither LIF, G-CSF, nor IL-6 could compete with the binding of labeled OSM to A375 cells.
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PMID:Oncostatin M is a differentiation factor for myeloid leukemia cells. 138 37

Differentiation choices in the haemopoietic and nervous systems are controlled in part by instructive factors. The cholinergic differentiation factor (CDF, also known as leukaemia inhibitory factor, LIF) affects the development of cultured cells from both systems. To understand the role of CDF/LIF during normal development in vivo, we have begun to localize its mRNA in the late fetal and postnatal rat. Application of reverse transcriptase-polymerase chain reaction and RNase protection methods reveals that CDF/LIF mRNA levels are developmentally modulated in both haemopoietic and neural tissues. A target tissue of cholinergic sympathetic neurons, the footpads that contain the sweat glands, express high levels of this mRNA (relative to mRNA for actin and beta 2-microglobulin). Levels in targets of noradrenergic neurons are lower, but do undergo significant changes during development. Signals are also detected in selective regions of the adult brain, and in embryonic skeletal muscle. This finding in muscle may be significant for motor neurons, because CDF/LIF is a trophic factor for these neurons in culture. Embryonic liver, neonatal thymus and postnatal spleen express CDF/LIF mRNA, and expression in gut is the highest of all tissues examined. The selective tissue distribution and developmental modulation of CDF/LIF mRNA expression support a role for this factor in the normal development of several organ systems.
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PMID:Further studies of the distribution of CDF/LIF mRNA. 142 9

The expression of the leukemia inhibitory factor/D factor (LIF) gene in human T-cell leukemia virus type 1 infected T-cell lines was examined. Human T-cell leukemia virus type 1 infected T-cell lines MT-1, MT-2, H89-59, H89-79, and H109 expressed LIF mRNA, but the T-cell lines MOLT-4 and TALL-1 did not. LIF mRNA expression was enhanced by interleukin 2 or 12-O-tetradecanoylphorbol-13-acetate in MT-2 cells. The biological activity of LIF was detected in culture medium enhanced by interleukin 2 in MT-2 cells. The expression of LIF mRNA was suppressed by 1 alpha,25-dihydroxyvitamin D3 and dexamethasone. These results imply that the expression of the LIF gene is involved in the development of hypercalcemia and abnormalities of the immune system observed in patients with adult T-cell leukemia.
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PMID:Expression and regulation of the leukemia inhibitory factor/D factor gene in human T-cell leukemia virus type 1 infected T-cell lines. 145 88

The interactions of purified recombinant human leukemia inhibitory factor (LIF), interleukin-6 (IL-6), granulocyte colony stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) on the clonogenicity of HL60 cells and U937 cells were studied in vitro. IL-6 alone strongly suppressed colony formation by U937 cells with induction of differentiation and loss of clonogenicity. GM-CSF interacted synergistically with IL-6 to further reduce colony number and suppress the growth of clonogenic cells formed by HL60 and U937 cells. LIF synergized with IL-6 to reduce colony number and enhance the suppression of the clonogenic U937 cells. The results suggest that these 4 glycoproteins, acting alone or in combination, may be able to suppress human leukemia cells of appropriate type and be of value in the clinical management of myeloid leukemia.
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PMID:Enhanced suppression of human myeloid leukemic cell lines by combinations of IL-6, LIF, GM-CSF and G-CSF. 168 77

A protein variously termed leukemia inhibitory factor (LIF), differentiation-inducing factor, differentiation inhibitory activity or human interleukin for DA cells can control the differentiation and proliferation of hematopoietic cells as well as of several other cellular lineages. In order to further elucidate the spectrum of LIF-producing cells, we examined different cell types for the expression of LIF mRNA using Northern blot analysis. LIF mRNA was detected in activated normal human T-cells and in two T-cell lines but was undetectable in a B-lymphoid cell line, in both resting and activated normal human granulocytes and monocytes and in human myeloid cell lines K562 and HL-60. In human lung fibroblasts and in human umbilical vein endothelial cells, LIF was constitutively expressed and its accumulation was increased in a time-dependent manner following treatment with the phorbol ester TPA and in the presence of the two immediate response cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1-beta. We conclude that mRNA for LIF is not only expressed by T-cells but also in human mesenchymal cells. Expression of LIF transcripts in these cells is constitutive and can be significantly enhanced by phorbol ester, TNF-alpha and IL-1-beta.
Leukemia 1991 May
PMID:Expression of leukemia inhibitory factor is regulated in human mesenchymal cells. 190 79

The in vitro action of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D arabinofuranosylcytosine (ara-C) was studied on the human leukemia cell line U 937. Parameters investigated included monitoring of transcript levels of the proto-oncogenes C-MYC, C-FOS, and C-FMS, and analysis of nitroblue tetrazolium (NBT) reduction and of surface expression of the C3 bi receptor. Furthermore clonal proliferation of U 937 cells was assessed in soft agar cultures. The results indicate that both agents have only little effects on U 937 cells when acting alone. When combined in culture, however, they synergize to induce monocytic differentiation of U 937 cells as disclosed by significant increase of cells capable of reducing NBT and displaying surface C3 bi receptor that was accompanied by reduction of clonogenicity in colony assays. Induction of differentiation and inhibition of proliferation of U 937 cells was preceded by downregulation of transcript levels of C-MYC, increase of C-FOS mRNA, and induction of accumulation of C-FMS mRNA. By sequential use of LIF and ara-C we also demonstrate that the basis of synergism of both agents does not involve mechanisms at the level of receptor ligation but that synergism may be initiated by complementary intracellular metabolic cascades.
Leukemia 1990 Sep
PMID:Synergistic effect of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D-arabinofuranosylcytosine (Ara-C) on proto-oncogene expression and induction of differentiation in human U 937 cells. 214 31

The in vitro actions of leukemia inhibitory factor (LIF) purified from Krebs tumor conditioned medium, were analyzed on murine leukemic M1 and WEHI-3B D+ cells and on normal hemopoietic progenitor cells. LIF has no observable effects on WEHI-3B D+ cells but rapidly induced macrophage differentiation and loss of clonogenicity in M1 cells, resulting in the formation of abortive clones or differentiating colonies of reduced size and number. These effects were observable within one to two cell divisions in the presence of LIF and were irreversible. Addition of macrophage-colony-stimulating factor (CSF) but not granulocyte/macrophage-CSF, granulocyte-CSF, or multi-CSF reduced the LIF-induced suppression of colony numbers and size. G-CSF had a slower differentiation-inducing action on M1 cells than LIF but potentiated the differentiation-inducing effects of low concentrations of LIF. LIF had no colony-stimulating activity for normal granulocyte-macrophage progenitor cells and did not alter their quantitative responsiveness to CSF. However, culture of normal progenitor cells in the presence of LIF, but initial absence of CSF, reduced the survival of these cells. The differing actions of LIF and G-CSF on M1 leukemic cells suggest the existence of distinct mechanisms for inducing macrophage differentiation in these leukemic cells.
Leukemia 1988 Apr
PMID:Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal murine hemopoietic cells. 245 26

The in vitro actions of recombinant human leukemia inhibitory factor (LIF) were studied on the human leukemia cell lines HL60 and U937. Parameters analyzed were the suppression of stem cell generation using sequential clonal cultures, alterations of surface antigen expression, and morphological changes. When acting alone, LIF had no observable effects on the number, size, or morphology of colonies formed by HL60 or U937 cells, surface phenotype expression, or recloning capacity of cells of either line. In combination with GM-CSF and G-CSF, however, LIF significantly reduced the number of colonies formed in agar respectively by HL60 and U937 cells. GM-CSF alone greatly reduced the clonogenicity of U937 cells. Using sequential recloning, marked suppression of clonogenicity was observed using combinations of LIF with GM-CSF in HL60 cultures and with G-CSF in U937 cultures. These results suggest that human LIF may have some capacity to suppress human leukemia cells with loss of clonogenicity, at least in combination with G-CSF or GM-CSF.
Leukemia 1989 Apr
PMID:Clonal suppression of HL60 and U937 cells by recombinant human leukemia inhibitory factor in combination with GM-CSF or G-CSF. 246 45

The gene for human leukemia inhibitory factor (LIF) has been mapped by Southern analysis of a series of mouse/human somatic cell hybrids and by in situ hybridization to the chromosomes of two normal males and some individuals with chromosomal rearrangements. The gene maps to 22q11-q12.2, between the Philadelphia translocation BCR gene and the breakpoint of the translocation in cell line GM2324 at 22q12.2. From the grain distribution over high resolution chromosome preparations, the most likely location is 22q12.1----q12.2. Southern analysis of DNA from one Ewing sarcoma with t[11;22][q24;q12] showed that the breakpoint on chromosome 22 is more than 15 kb 5' or 8 kb 3' from the LIF gene. The location of the LIF gene indicates that translocations of this gene are unlikely to play a role in myeloid leukemia and myeloproliferative disorders.
Leukemia 1989 Jan
PMID:The gene for human leukemia inhibitory factor (LIF) maps to 22q12. 249 97

Differentiation-competent clones of myeloid leukemic cells, independently isolated from the M1 cell line in Rehovot, Israel, and in Saitama, Japan, can be induced to differentiate to mature cells by the protein which we called macrophage and granulocyte differentiation-inducing protein-2 (MGI-2) that we have shown is interleukin 6 (IL-6). We now show that our MGI-2/IL-6-susceptible clones of M1 cells were not induced to differentiate with the differentiation-inducing protein called D-factor/leukemia inhibitory factor (LIF) which has also been called human interleukin for DA cells (HILDA), whereas this protein induced differentiation to macrophages in the M1 clone isolated in Saitama which was also used in Melbourne, Australia, The D-factor/LIF susceptible clone also showed a 4-fold lower sensitivity to MGI-2/IL-6 than the D-factor/LIF resistant clone. Both types of clones differentiated with interleukin-1 alpha (IL-1 alpha) and dexamethasone, whereas the D-factor/LIF resistant clone, but not the D-factor/LIF susceptible clone, was induced by bacterial lipopolysaccharide (LPS) to differentiate to mature macrophages. The present results show that clonal differences in susceptibility to differentiation-inducing proteins in the M1 cell line can explain the isolation of different differentiation-inducing proteins in M1 leukemic cells in different laboratories.
Leukemia 1989 Nov
PMID:Clonal variation in susceptibility to differentiation by different protein inducers in the myeloid leukemia cell line M1. 250 27


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