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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

cDNA clones encoding the human leukaemia inhibitory factor (hLIF) receptor were isolated by screening a placental cDNA expression library in COS-7 cells with 125I-hLIF. The cloned LIF receptor is a member of the haemopoietin receptor family and comprises a signal sequence (44 amino acids), an extracellular region of two haemopoietin receptor domains and three fibronectin type III domains (789 amino acids), a transmembrane domain (26 amino acids) and a cytoplasmic domain (238 amino acids). The LIF receptor is expressed in COS-7 cells as a 190 kDa glycoprotein that specifically binds human LIF with low affinity, but does not bind mouse LIF. Clones encoding a soluble form of the homologous mouse LIF receptor have been isolated, suggesting complex interactions between the various forms of LIF ligand and receptor in vivo. The LIF receptor is most related to the gp130 signal-transducing component of the IL-6 receptor, a feature that may provide a molecular basis for the intertwined biologies of LIF and IL-6 in the absence of obvious structural similarly between the ligands. Mouse B9 plasmacytoma cells transfected with the human LIF receptor display novel high affinity LIF receptors that are presumed to consist of transfected receptors in association with endogenous mouse high affinity-converting subunits. Unlike the low affinity human LIF receptor, the mixed species high affinity receptor is capable of binding mouse LIF.
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PMID:Reconstitution of high affinity leukaemia inhibitory factor (LIF) receptors in haemopoietic cells transfected with the cloned human LIF receptor. 142 17

Mouse kidney induction proceeds in vitro much as it does in vivo: the ureteric bud bifurcates to give collecting ducts while the mesenchyme condenses into aggregates which epithelialise and then elongate into tubules with glomerular and other nephron structures. We report here that the factor known as LIF (leukaemia inhibitory factor), which regulates the differentiation and growth of embryonic-stem (ES) and other cells in culture, has little effect in vitro on growth or on ureteric-bud morphogenesis other than to stimulate the bifurcation process. It does however exert a striking effect on the mesenchyme. At about four times the concentration required to inhibit ES-cell differentiation, LIF strongly but reversibly blocks the effects of metanephric mesenchyme induction: although mesenchyme condenses around growing duct tips, the number of mature nephrons that form over 6 days is reduced by 75% or more. The few nephrons that do develop in the presence of LIF probably come from mesenchyme already induced at the time of culture and are indistinguishable from those that form in controls as assayed by morphology, by X-gal staining of endogenous galactosidase and by antibodies to brush-border and CD15 antigens. There is a further unexpected feature of rudiments cultured in LIF which is absent in controls: they contain an unexpectedly high number of stable epithelialised aggregates that express laminin around their periphery and which do not develop further. These results argue that the process of nephrogenesis involves at least two distinct stages which can be blocked by LIF: the effect of the initial induction and the future development of epithelialised aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LIF, the ES-cell inhibition factor, reversibly blocks nephrogenesis in cultured mouse kidney rudiments. 176 94

A murine megakaryoblastic cell line growing in protein-free culture (L8057Y5) was established from an experimentally induced murine leukemia (MK8057). Most of the Y5 cells were small and blast-like, with 2-4N in DNA content. Also, large cells possessing a lobulated nucleus characteristic of megakaryocytes, which showed polyploidization to more than 4N up to 16N, were occasionally seen. Nearly 5% of the total number of Y5 cells were positive for acetylcholinesterase reaction. The survival time of C3H/He mice after injection with Y5 cells was longer than that of mice injected with the original MK8057 cells. The colony-forming ability of Y5 cells in the spleen of the lethally irradiated mouse was much lower, whereas the number of in vitro colonies derived from Y5 was greater than that of MK8057. The plating efficiency of colony formation in serum-free methylcellulose culture was higher at a low O2 tension. Conditioned medium of Y5 cells enhanced colony formation as well as 3H-TdR uptake by Y5 cells, which implies that Y5 cells may produce autocrine growth factor(s). mRNAs for IL-6, LIF, and INF-gamma were expressed in Y5 cells; these cytokines may have roles in the growth mechanisms of the cell line.
Leukemia 1991 May
PMID:Establishment and characterization of a murine megakaryoblastic cell line growing in protein-free culture (L8057Y5). 190 80

The mammalian embryo develops as a quasi-stem cell system whose differentiation and pluripotentiality in vitro is controlled by a single regulatory factor, Differentiation Inhibiting Activity/Leukemia Inhibitory Factor (DIA/LIF). DIA/LIF is expressed in two distinct functional forms, derived from the use of alternate transcriptional start sites, one of which is freely diffusible and the other tightly associated with the extracellular matrix. The dissemination of the DIA/LIF signal is therefore under specific molecular control. The expression of DIA/LIF in vitro is both developmentally programmed and controlled by the action of other growth factors, the most notable of which are members of the fibroblast growth factor family expressed by the stem cells themselves. This indicates that differentiation and proliferation in early development of the mouse are controlled, at least in part, by an interactive network of specific growth and differentiation regulatory factors.
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PMID:Growth and differentiation factors of pluripotential stem cells. 212 87

The regulatory factor Differentiation Inhibiting Activity/Leukaemia Inhibitory Factor (DIA/LIF) suppresses the differentiation of cultured embryonic stem (ES) cells. In the present study, it is shown that ES cell lines can be derived and maintained in the absence of feeder layers using medium supplemented with purified DIA/LIF. These cells can differentiate normally in vitro and in vivo and they retain the capacity for germ-line transmission. DIA/LIF therefore fulfils the essential function of feeders in the isolation of pluripotential stem cells.
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PMID:Establishment of germ-line-competent embryonic stem (ES) cells using differentiation inhibiting activity. 212 26

Purified recombinant granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) stimulated the formation of similar numbers of colonies in cultures of normal mouse marrow cells. LIF and IL-6 induced comparable differentiation in clonal cultures of murine M1 leukemic cells and exhibited enhanced actions in combination. However, LIF was 16-25-fold more active than IL-6. Induction of differentiation in M1 leukemic colonies by both LIF and IL-6 was enhanced by the addition of G-CSF or M-CSF but not by GM-CSF or Multi-CSF. Both G-CSF and IL-6, but not LIF, were able to induce differentiation in murine WEHI-3B leukemic colonies, but G-CSF was 10-fold more efficient than IL-6. Both G-CSF and IL-6 were able to stimulate the proliferation of cells of the NFS-60 continuous cell line, but G-CSF was 30-fold more efficient. M1 cells constitutively produced low levels of IL-6 and production was enhanced by LIF, but the general characteristics of the actions of LIF, IL-6, and G-CSF suggested that each operates independently as a direct differentiation inducer of leukemic cells. The similarities in the biology and actions of G-CSF, LIF, and IL-6 suggest that they may be designed to exhibit coordinated biological functions in certain situations.
Leukemia 1989 May
PMID:Actions and interactions of G-CSF, LIF, and IL-6 on normal and leukemic murine cells. 246 11

We have previously characterized, purified and cloned a novel murine and human regulator [leukaemia inhibitory factor, LIF] which induces the differentiation of certain murine and human myeloid leukaemic cells. Recently we have shown that there are specific LIF receptors on murine embryonic stem [ES] and embryonal carcinoma [EC] cells and that purified recombinant LIF can substitute for feeder cells and crude sources of differentiation inhibiting activity [DIA] [such as BRL-cell-conditioned medium] in the maintenance of ES cells in a pluripotential state in vitro. Furthermore, ES cells maintained in culture in recombinant LIF for a prolonged period can give rise to germline chimaeric mice. Thus, based on a number of biochemical and biological similarities, it is likely that LIF and DIA are the same molecule. The identification of LIF as a molecule, necessary and sufficient for the maintenance of ES cells in culture, should have a profound impact on the use of these cells for genetic manipulations.
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PMID:LIF: a molecule with divergent actions on myeloid leukaemic cells and embryonic stem cells. 251 64

Cultures of differentiated melanocytes can readily be grown from the dissociated epidermis of neonatal mice, and immortal cell lines often develop from these. However, the first cells that grow and transiently dominate the cultures, while similar to melanocytes, are unpigmented. These have been shown to be precursors of melanocytes and may be termed melanoblasts. Under our previous standard culture conditions, involving the use of keratinocyte feeder cells, foetal calf serum, the phorbol ester 12-O-tetradecanoyl phorbol acetate (TPA) and cholera toxin, all the melanoblasts spontaneously differentiated to pigmented melanocytes within about 3 weeks. We now describe some factors affecting the proliferation and differentiation of diploid murine melanoblasts in the presence of serum. Murine stem cell factor/steel factor (SCF), basic fibroblast growth factor (bFGF) and murine leukaemia inhibitory factor/differentiation-inhibiting activity (LIF/DIA) all increased melanoblast numbers. SCF and LIF also slightly inhibited melanoblast differentiation, while cholera toxin and TPA promoted differentiation. Using some of these findings, and by regular replacement of keratinocyte or fibroblastoid feeder cells, we have established a clonal line of immortal murine melanoblasts, 'melb-a'. These cells express tyrosinase-related protein-2 but not, in general, tyrosinase. They can be induced to differentiate irreversibly to functional melanocytes (also proliferative and immortal) by plating in the absence of feeder cells. Thus a new immortal melanocyte line, 'melan-a2', has also been produced.
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PMID:A cloned, immortal line of murine melanoblasts inducible to differentiate to melanocytes. 754 May 32

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


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