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 DNase I sensitivity of total chromatin was studied in fixed cells and nuclei isolated from proliferating and terminally differentiated cells, by measuring the incorporation of labelled nucleotides into DNase-sensitive sites, and electrophoresis of DNA isolated from DNase-treated nuclei. The unfixed nuclei were sensitive to digestion at around 10 micrograms/ml, the fixed cells at 30 ng/ml DNase I concentration. Proliferating Rauscher leukemia cells were more digestible than normal spleen cells. The DNase I sensitivity of the human HL60 leukemia line decreased upon DMSO-induced differentiation but still exceeded the digestibility of nuclei from normal human peripheral blood. A novel flow-cytometric technique was developed to study DNase sensitivity at the cell level. It confirmed the relative resistance of differentiated cells to DNase I and ruled out the possibility that this could be due to an altered distribution of cell cycle phases. The overall DNase I sensitivity of chromatin was compared with the sensitivity of the c-myc gene and the myc-associated hypersensitive sites. The latter sites were detected at 1 microgram/ml DNase I in HL60 nuclei. They disappeared partially upon DMSO-induced differentiation. At 10 micrograms/ml, myc was degraded in both growing and differentiating HL60, but not in HPB cells. These data suggest that a progressive condensation of the chromatin occurs during terminal differentiation which gradually involves specific genes that need to be inactivated.
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PMID:Overall changes in chromatin sensitivity to DNase I during differentiation. 346 2

Seven cellular loci with acceptor sites for retroviral integrations have been mapped for the presence of DNase I-hypersensitive sites in chromatin. Integrations in three of these loci, chicken c-erbB, rat c-myc, and a rat locus, dsi-1, had been selected for in retrovirus-induced tumors. Of the remaining four, two, designated dsi-3 and dsi-4, harbored acceptor sites for apparently unselected integrations of Moloney murine leukemia virus in a Moloney murine leukemia virus-induced thymoma, and two, designated C and F, harbored unselected acceptor sites for Moloney murine leukemia virus integrations in a rat fibroblast cell line. Each acceptor site mapped to within 500 base pairs of a DNase I-hypersensitive site. In the analyses of the unselected integrations, six hypersensitive sites were observed in 39 kilobases of DNA. The four acceptor sites in this DNA were localized between 0.05 and 0.43 kilobases of a hypersensitive site. The probability of this close association occurring by chance was calculated to be extremely low. Hypersensitive sites were mapped in cells representing the lineage in which integration had occurred as well as in an unrelated lineage. In six of the seven acceptor loci hypersensitive sites could not be detected in the unrelated lineage. Our results indicate that retroviruses preferentially integrate close to DNase I-hypersensitive sites and that many of these sites are expressed in some but not all cells.
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PMID:Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. 349 May 82

The c-myc gene product is a nuclear protein expressed in a wide variety of cell types. It has been implicated in the control of normal cell growth as well as transformation, but its exact function is unknown. When the human promyelocytic leukaemia cell line HL60 is treated with retinoic acid, the cells differentiate into granulocytes, and there is a reduction in steady state c-myc RNA of more than 10-fold. Nuclear runoff assays show that this reduction is caused by a corresponding decrease in the transcription of exon 2. However, only a minor decrease in exon 1 transcription is observed upon differentiation. In undifferentiated HL60 cells there is an approximately 3-fold molar excess of exon 1 transcription over exon 2, and this excess increases to about 15-fold in differentiated cells. This observation suggests that a major component of c-myc transcriptional down-regulation in HL60 cells is at the level of elongation rather than at the level of initiation. The position of the elongation block was mapped to the region of the boundary between exon 1 and intron 1. During HL60 differentiation, a DNase I hypersensitive site in the chromatin about 300 bases downstream of the 5' end of of intron 1 increases in intensity relative to other sites, possibly reflecting events associated with the termination of transcription. Our runoff analysis also revealed transcription of both strands immediately upstream of exon 1 in HL60 cells. The sense strand transcription of this region produces a novel c-myc RNA which initiates several hundred bases upstream of the previously defined promoters and is found in a variety of cell types.
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PMID:A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. 352 Mar 40

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

A Moloney murine leukemia virus-derived retroviral vector (N4) carrying the bacterial neomycin resistance gene (neo) was used to study the chromatin configuration of integrated proviral DNA in NIH 3T3-derived cell lines containing one copy of the vector DNA per cell. Three independently obtained cell lines were examined. In two of these cell lines, the vector was introduced by viral infection, while in the third the construct was introduced by DNA transfection. Such transfected cell lines (including the one examined) usually express 10- to 50-fold less virus-specific RNA than do cell lines obtained by viral infection. All three cell lines exhibited similar patterns of DNase I-hypersensitive (HS) sites. Two strong DNase I HS sites were detected in the 5' long terminal repeat, which contains signals required for proper and efficient initiation of viral transcription. One of these sites was found to overlap the viral enhancer sequences, while the other site mapped very close to the start site for viral transcription. A third HS site was detected in nearby internal viral sequences. Only one HS site was found in the 3' long terminal repeat, which contains the signal(s) required for proper addition of a poly(A) tail to viral transcripts. This HS site was located in the region of the viral enhancer. Several weak DNase I HS sites were also found in the cellular sequences adjacent to the integration sites, at different locations in each cell line analyzed. No common pattern of cellular DNase I HS sites was found. These observations suggest that the 5' and 3' long terminal repeats of integrated retroviral proviruses exhibit different chromatin conformations, possibly reflecting the different functions encoded by the otherwise identical sequences, and the DNase I HS sites detected in these studies reflect only a potential for transcription and are not a reflection of the high transcriptional activity characteristic of retroviruses.
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PMID:Significance of DNase I-hypersensitive sites in the long terminal repeats of a Moloney murine leukemia virus vector. 357 42

We have surveyed 22 kb of DNA from the region surrounding the human fetal (gamma) globin genes and have identified one fragment that meets all of the criteria for a non-tissue specific enhancer element. The enhancer-containing fragment starts approximately 400 bp 3' to the polyadenylation signal of the A gamma gene and is less than 750 bp in length. Addition of this fragment to plasmids containing a 'gamma-CAT' hybrid gene [consisting of the gamma globin gene promoter fused to the chloramphenicol acetyl transferase (CAT) gene] increases CAT expression 6-23-fold in K562 erythroleukemia cells, depending upon the method of transfection. The increase in expression is essentially independent of the orientation or position of the fragment with respect to the gamma-CAT hybrid gene. The 3' gamma enhancer activates heterologous promoters in erythroleukemia cells, and is also active in non-erythroid cell lines. The enhancer acts by increasing the number of transcripts initiated from the normal gamma globin gene transcription initiation site. The enhancer region contains two DNase I hypersensitive sites in erythroleukemia cells but none in nonerythroid human leukemia cell lines. The 3' gamma globin gene enhancer contains a unique element that is similar to sequences found in an enhancer 3' to the chicken beta globin gene, suggesting that this conserved element may have a role in enhancer function.
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PMID:An enhancer element lies 3' to the human A gamma globin gene. 369 78

Transcription of unrearranged kappa constant region (kappa 0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase kappa 0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged mu heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the kappa enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of kappa transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate kappa transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.
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PMID:Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis. 392 1

A method is presented whereby antigenic determinants recognized by specific monoclonal antibodies can be mapped to specific sites on a protein sequence with high resolution. Short DNase I-generated DNA fragments encoding portions of the protein of interest are molecularly cloned into the EcoRI site of the beta-galactosidase gene of phage lambda Charon 16 so as to obtain expression of random protein fragments as fusion proteins. The monoclonal antibody is used to screen the phage library to isolate phage expressing the specific antigenic determinant. DNA of immunoreactive phage can be analyzed rapidly and subcloned to allow DNA sequence determination. The method is generally applicable and permits antigenic determinants of functionally interesting monoclonal antibodies to be mapped and related to specific protein sequences. We have used this procedure to determine the region of the feline leukemia virus envelope protein gp70 recognized by a virus-neutralizing monoclonal antibody, cl.25. Antibody binding was mapped to a 14-amino acid region in the amino-terminal half of gp70. This region may be directly involved in an essential function of the gp70 protein, perhaps in gp70-mediated host recognition functions. Synthetic peptides derived from this region may provide useful vaccine antigens for the prevention of feline leukemia virus-associated disease in cats.
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PMID:Method to map antigenic determinants recognized by monoclonal antibodies: localization of a determinant of virus neutralization on the feline leukemia virus envelope protein gp70. 620 25

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

We have mapped the DNase I-hypersensitive sites around the epsilon-globin and c-myc genes in two human leukemia cell lines K562 and HL60. In K562 cells in which the epsilon-globin gene is transcribed, six DNase I-hypersensitive sites are found in 6 kilobases (kb) of upstream flanking DNA; in HL60 cells in which the c-myc gene is expressed, two DNase I-hypersensitive sites are observed in 2 kb of upstream DNA. Neither the inactive epsilon-globin gene in HL60 cells nor the inactive c-myc gene in K562 cells displays such upstream DNase I-hypersensitive sites. Our results are consistent with previous studies that have shown DNase I-hypersensitive sites within 1 kb of the 5' end of other expressed genes. In addition, we have found sites displaying even more DNase I sensitivity further upstream of expressed epsilon-globin and c-myc genes. Among the six DNase I-hypersensitive sites of the expressed epsilon-globin gene in K562 cells, the most sensitive site is located about 6 kb upstream of the epsilon-globin gene. When correlated with the DNA sequence upstream of the epsilon-globin gene, this site was found to correspond to a region that contains a stretch of 28 consecutive Ts, three enhancer core-like sequences, and a stretch of consecutive (C-A)15(T-A)6 alternating purine and pyrimidine bases. These findings suggest the possibility that an enhancer element for epsilon-globin gene expression resides within this DNase I-hypersensitive site.
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PMID:Mapping of DNase I-hypersensitive sites in the upstream DNA of human embryonic epsilon-globin gene in K562 leukemia cells. 623 14


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