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)

The erythroleukemia cell line IW32, derived by transformation with the Friend murine leukemia virus, has been shown previously to produce erythropoietin (EPO) constitutively. Here we demonstrate that, in addition to the normal mouse EPO locus, this cell line has another EPO locus which has undergone rearrangement and amplification. Both loci were cloned, and the rearrangement breakpoint of the second EPO locus was located within a 1.1-kilobase region upstream of an otherwise apparently normal EPO gene. There are no viral sequences present in the immediate vicinity of the rearranged EPO gene. DNase I digestion studies suggest that the rearranged gene is in a region where the chromatin is more sensitive to DNase hydrolysis than is the site of the normal gene. We conclude, tentatively, that the rearranged EPO locus is probably the transcriptionally active one and that either proviral sequences are acting at a distance to activate the EPO gene or the rearrangement itself has served to activate the gene.
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PMID:Rearrangement and expression of erythropoietin genes in transformed mouse cells. 356 95

The gibbon ape leukemia virus (GALV) contains enhancer activity within its long terminal repeat. In the GALV Seato strain this activity resides in a 48-base-pair (bp) repeated element. We demonstrate the existence of a cellular protein which binds in this region of the Seato strain. A sensitive method for enriching protein-DNA complexes from crude extracts coupled with exonuclease and DNase footprint analysis revealed the specific binding of this protein to a 21-bp region within each repeated element. A 22-bp oligonucleotide fragment defined solely by the 21-bp footprint binds a protein in vitro and displays enhancer activity in vivo, suggesting that this protein is a major determinant of GALV enhancer activity. The protein is present in three cell lines which are positive for enhancer activity and is not detected in Jurkat cells, which are negative for enhancer activity. Only GALV long-terminal-repeat variants which support high levels of enhancer activity in vivo compete with this protein for specific binding in vitro, suggesting a potential role for the protein in determining enhancer activity. This protein binding is not inhibited by competition with heterologous retroviral enhancers, demonstrating that it is not a ubiquitous retroviral enhancer binding protein.
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PMID:Binding of a cellular protein to the gibbon ape leukemia virus enhancer. 367 Feb 91

Mov13 mice carry a single Moloney murine leukaemia virus (M-MuLV) proviral copy in the first intron of the alpha 1(I) collagen gene. Virus insertion interferes with the synthesis of stable alpha 1(I) collagen messenger RNA and causes a recessive lethal mutation. The virus insertion has induced changes of the methylation pattern as well as the chromatin conformation in the mutated gene. Specifically, a DNase-hypersensitive site which is associated with active transcription of the wild-type collagen gene is not present in the mutant allele. The block of collagen expression could be caused by virus-induced instability of collagen mRNA or by impaired initiation of transcription. To distinguish between these possibilities, we have compared the activity of the alpha 1(I) collagen gene promoter in cell lines derived from wild-type and Mov13 embryos by nuclear run-on transcription experiments and S1 mapping of nuclear RNA. We show here that initiation of transcription of the mutant gene is reduced 20-100-fold. This indicates that the virus-induced change of chromatin structure in the promoter region of the mutant gene prevents RNA polymerase from binding to its DNA template. Our results are consistent with the notion that the promoter-associated DNase-hypersensitive site is a prerequisite for rather than a consequence of gene activity.
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PMID:Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. 396 Jan 20

1. Nilemycin (NM) is found to exert an inhibitory effect on the mouse tumor Sarcoma 180 near toxic doses but not with Leukemia 1210. 2. In Yoshida rat sarcoma cells NM inhibits cellular de novo nucleic acid synthesis and protein to a much lesser extent. 3. More than 50% inhibition by NM to de novo synthesis of RNA, in a system using calf thymus DNA as a template, could be observed. 4. Suitable levels of NM reduce the S values of DNA. 5. The antibiotic induced metachromatic changes in the u.v. spectrum of DNA solutions. 6. NM markedly inhibited the polynucleotide ligase repairing action on DNase-1-nicked DNA. 7. It is presumed that NM intercalates nicked DNA into such a configuration that the reactive sites of the polynucleotides are inaccessible to the ligase activities.
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PMID:Nilemycin, an intercalating agent for deoxyribonucleic acid. 618 40

Nuclei were isolated from various cell types including Chinese hamster ovary (CHO) and L1210 leukemia cell lines, primary cultures of fibroblasts, nonstimulated and stimulated human lymphocytes and mouse liver cells, by using different isolation techniques. The isolated nuclei were subsequently stained with acridine orange (AO) and their fluorescence was measured by flow cytometry. Various procedures designed to stain DNA versus RNA differentially with AO were tested, and the staining of isolated nuclei was compared with that of whole cells. Control incubations with RNase and DNase were performed to estimate in whole cells and in nuclei the contribution of DNA and RNA to the fluorescence intensity at the respective wavelength bands of maximum emission for DNA (F530) and RNA (F greater than 600). Depending on the cell type, 10-20% of total cell RNase-sensitive F greater than 600 is localized in the nuclei. The RNase-resistant portion of F greater than 600 of isolated nuclei represents the stainability of DNA. Suppression of cell proliferation in subconfluent cultures results in a decrease in both whole cell and in nuclear RNA content. Nonstimulated lymphocyte nuclei have considerably lower RNA content than nuclei from lymphocytes stimulated by pokeweed mitogen. Two subpopulations of nuclei having the same (2C) DNA content but differing in RNA content, are present in mouse liver; the cells entering S phase originate from the high RNA population.
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PMID:RNA and DNA content of isolated cell nuclei measured by multiparameter flow cytometry. 618 86

L1210 leukemia cell cytosol was analysed for the presence of DNase I activity. No free activity was determined in crude cytosol. DNase I enzyme was found to occur in a latent form bound to cytoplasmic actin. DNase-actin complex was partially isolated by Sephadex filtration and DNase I-like activity was demonstrated after SDS gel electrophoresis of the complex and enzyme renaturation. The results were compared with those for synthetic complex of pancreatic bovine DNase I and chicken muscle actin.
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PMID:Evidence for the presence of DNase-actin complex in L1210 leukemia cells. 621 6

Glucocorticoid-specific binding macromolecules were measured and characterized in L2C cells, a B-lymphocyte guinea pig leukemia that is resistant to administered cortisol or adrenocorticotrophic hormone. L2C cells were harvested by cardiac puncture followed by Ficoll:Hypaque separation techniques. The cells were lysed by sonication, and the cytosol was obtained after centrifugation at 106,000 x g for 60 min at 0 degrees. Cytosol glucocorticoid receptor measurements were obtained by hydroxylapatite assay or column chromatography using Sephadex G-25. Maximal specifically bound [3H]triamcinolone acetonide in the cytosol fraction was 300 fmol/10(8) cells. Scatchard plot of specific L2C cytosol binding gave a Kd of 18 nM and an estimate of 2000 binding sites/cell. The specificity of binding in L2C cytosol was triamcinolone acetonide > dexamethasone > cortisol > progesterone > testosterone = estradiol. Binding of [3H]triamcinolone acetonide to cytosol glucocorticoid receptors was maximal at 22 hr of incubation at 19 degrees, and the receptor complex was stable for 48 hr. The receptor complex was not affected by DNase or RNase, but the receptor complex was lost with pronase or heat denaturation. Whole-cell binding assays were also performed, which resulted in similar quantities of maximally bound glucocorticoid receptor as well as the specificity of binding of various hormone analogs as found in the cytosol receptor assays. Transferring the whole cells from 0 to 22 degrees resulted in the appearance in nuclei of approximately 65% bound receptors. However, these translocated receptor complexes do not appear to affect the viability of the L2C cells as measured by trypan blue exclusion.
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PMID:Characterization of glucocorticoid-specific binding in the L2C leukemia. 693 47

The binding of [3H]dexamethasone to the cytosol fraction prepared from the human leukemia cell line K562 was studied with a competitive binding assay. Specific, saturable binding was identified by incubating cytosol with increasing concentrations of [3H]dexamethasone in the presence and absence of nonlabeled dexamethasone. A Scatchard plot of the data was linear, suggesting the presence of a single class of binding sites with KD = 2.49 +/- 0.23 x 10(-8)M. The binding sites appear to be protein in nature, since specific binding was reduced by treatment of the cytosol with trypsin, pronase, and heat; neither DNase nor RNase affected the binding. Binding was also reduced in the absence of alpha-thioglycerol and in the presence of p-chloromercuribenzoate and N-ethylamaleimide, suggesting that optimal binding activity requires reduced sulfhydryl groups. The binding site appears to be specific for glucocorticoids as evaluated in competition studies. Finally, glucocorticoids were found to inhibit the clonal growth of K562 cells in vitro, suggesting a potential role for glucocorticoid binding sites in the modulation of K562 cell proliferation.
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PMID:Identification of a glucocorticoid receptor in the human leukemia cell line K562. 720 98

Programmed cell death is activated, by different stimuli and in many cell types, to regulate cell population balance during tissue proliferation and embryogenesis. Its initial event seems to be, in most cases, the activation of a Ca(2+)-dependent endonuclease, causing DNA cleavage into nucleosomic fragments. Its morphological expression is characterized by deep nuclear changes, consisting of typical cap-shaped chromatin marginations, followed by nuclear fragmentation and final formation of numerous micronuclei. Cytoplasmic damage appears in a very late stage of the process and the greatest part of the phenomenon appears to take place despite good preservation of the plasma membrane and organellar component. In the present study we analyzed apoptosis in camptothecin-treated HL60 leukaemia cells, and in freshly isolated mouse thymocytes treated with dexamethasone. The process was first quantified and time monitored by flow cytometry. Subsequently the specimens were processed for morphological examination in order to investigate the behaviour of the different nuclear domains. To follow DNA and RNA localization, we utilized osmium ammine and DNase-colloidal gold cytochemical reactions. The concentration of most DNA in the cap-shaped structures was demonstrated by these reactions. Confocal microscopy of cells processed by in situ nick-translation suggested that DNA was firstly cleaved and subsequently condensed in cup-shaped structures. Despite the strong nuclear modifications, nucleoli could be clearly recognized until the late apoptotic stages.
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PMID:The behaviour of nuclear domains in the course of apoptosis. 786 64

We have investigated the mechanism whereby nuclear DNA fragmentation activity emerging during early apoptosis is inhibited during normal cell life. In a cell-free system, cytosol fractions from diverse nonapoptotic human cell lines (Jurkat T-cell leukemia, HeLa carcinoma, SK-N-MC neuroblastoma, and WI-38 embryonic lung fibroblast) potently neutralized the nuclear DNA fragmentation activity of cytosol from apoptotic anti-Fas treated Jurkat cells. Recombinant human DNA fragmentation factor 45 kDa subunit (DFF45/ICAD), an inhibitor of the caspase-activated DNase DFF40/CAD, substituted for healthy cytosol in inhibiting DNA fragmentation. An antiserum against human DFF45 detected 44 and 34 kDa proteins (major and minor, respectively) in the cytosols but not in the nuclear or membrane fractions of various cultured human cells. Cytosols depleted of DFF45/ICAD by immunoadsorption had little or no inhibitor of nuclear DNA fragmentation activity and no caspase-activated DNA fragmentation activity. We conclude that immunoreactive DFF45/ICAD is the principal inhibitor of apoptotic DNase activity in the cytosol of healthy cells.
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PMID:Inhibition of apoptosis-associated DNA fragmentation activity in nonapoptotic cells: the role of DNA fragmentation factor-45 (DFF45/ICAD). 987 36


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