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 sensitive exonuclease assay revealed multiple sites for interaction, in vitro, of sequence specific factors with c-myc upstream elements. At one site, more than 1500 base pairs upstream of the c-myc promoter P1, binding activity was lost as dimethyl sulfoxide (Me2SO) induced shut-off of c-myc expression in HL-60 and U-937 leukemia cells. The disappearance of other specific binding activities was not noted. In addition, the binding activity was noted to be cell-line specific. The sequence binding the Me2SO-regulated factor was precisely located allowing confirmation of the temporal pattern of regulation by electrophoretic mobility shift analysis. Because the binding activity was most abundant before the decrease of c-myc expression during differentiation, it was inferred that the far upstream element (FUSE) served a positive role, potentiating c-myc expression. A 4-base pair deletion which eliminated binding to FUSE also reduced expression of a transfected, chimeric c-myc-CAT gene in untreated, but not in Me2SO-treated U-937 cells. FUSE and its binding protein may contribute to cell line- and differentiation-specific modes of c-myc regulation.
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PMID:A far upstream element stimulates c-myc expression in undifferentiated leukemia cells. 221 18

Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
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PMID:Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. 238 34

To determine the block(s) to spleen necrosis virus (SNV) replication in mouse cells, we studied the expression of a dominant selectable marker, neo, or a gene whose product is easily assayed, the chloramphenicol acetyltransferase (cat) gene, in SNV-derived and murine leukemia virus-derived vectors. Using transient (CAT) and stable (Neor phenotype) transfection assays, we showed that the SNV promoter was used in mouse cells only when the 3' SNV long terminal repeat (LTR) was absent. Infection of mouse cells with recombinant SNV viruses was 1% as efficient as infection of permissive dog (D17) cells. The SNV proviruses in mouse cells appeared normal by Southern blot analysis, indicating that their integration probably occurred by normal mechanisms. S1 nuclease analyses of Neor mouse cell clones, each harboring a single recombinant SNV provirus, showed that the selected (internal) promoter was active, but that the 5' SNV LTR promoter was not. However, in the rare (less than 10(-6)) Neor colonies in which expression of the 5' LTR was selected, both promoters were active. Thus, the block to SNV infection of mouse cells is at least at two levels; one is a 100-fold-decreased efficiency at some step(s) up to and including integration, and the other is at transcription.
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PMID:Transcription from a spleen necrosis virus 5' long terminal repeat is suppressed in mouse cells. 244 16

To study the regulation of MHC class I gene expression during embryonic development, we have characterized a number of clonal cell lines derived from somite stage mouse embryos that were established with or without infection by several transforming retroviruses in combination with murine leukemia viruses. Unlike embryonal carcinoma (EC) cells that have been used as a model for early embryos, the cell lines derived from somite stage embryos are negative for stage specific embryonic Ag-1 and do not appear to differentiate after retinoic acid treatment. Morphology varies from clone to clone and is distinct from that of F9 and other EC cells. In agreement with previous findings in in vivo embryos, expression of surface MHC class I antigen in 57 new clones is either undetectable or low (with variability). All of the clones respond to the addition of interferons and express MHC class I antigens at high levels, but the kinetics of mRNA accumulation vary considerably. To examine the basis of the generally low or absent MHC class I gene expression in these cells, we tested promoter activity of a MHC class I gene by CAT assay after transient DNA transfection. Regardless of the basal levels of mRNA or surface Ag, CAT activity directed by various portions of the 5' flanking region of the MHC class I gene was uniformly low. The cells showed neither the negative nor the positive regulation of MHC class I genes that had been noted respectively for EC cells and for cells expressing the Ag constitutively. The pattern seen in the new cell lines suggests that there is an intermediate stage in the developmental regulation of MHC class I gene expression that may operate during the middle to late stage of fetal development.
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PMID:Establishment of cell lines from somite stage mouse embryos and expression of major histocompatibility class I genes in these cells. 245 81

Deletion analysis offers a powerful alternative to linkage and karyotypic approaches for human chromosome mapping. A panel of deletion hybrids has been derived by mutagenizing J1, a hamster cell line that stably retains chromosome 11 as its only human DNA, and selecting for loss of MIC1, a surface antigen encoded by a gene in band 11p13. A unique, self-consistent map was constructed by analyzing the pattern of marker segregation in 22 derivative cells lines; these carry overlapping deletions of 11p13, but selectively retain a segment near the 11p telomere. The map orders 35 breakpoints and 36 genetic markers, including 3 antigens, 2 isozymes, 12 cloned genes, and 19 anonymous DNA probes. The deletions span the entire short arm, dividing it into more than 20 segments and define a set of reagents that can be used to rapidly locate any newly identified marker on 11p, with greatest resolution in the region surrounding MIC1. The approach we demonstrate can be applied to map any mammalian chromosome. To test the gene order, we examined somatic cell hybrids from five patients, whose reciprocal translocations bisect band 11p13; these include two translocations associated with familial aniridia and two with acute T-cell leukemia. In each patient, the markers segregate in telomeric and centromeric groups as predicted by the deletion map. These data locate the aniridia gene (AN2) and a recurrent T-cell leukemia breakpoint (TCL2) in the marker sequence, on opposite sides of MIC1. To provide additional support, we have characterized the dosage of DNA markers in a patient with Beckwith-Wiedemann syndrome and an 11p15-11pter duplication. Our findings suggest the following gene order: TEL - (HRAS1, MER2, CTSD, TH/INS/IGF2, H19, D11S32) - (RRM1, D11S1, D11S25, D11S26) - D11S12 - (HBBC, D11S30) - D11S20 - (PTH, CALC) - (LDHA, SAA, TRPH, D11S18, D11S21) - D11S31 - D11S17 - HBVS1 - (FSHB, D11S16) - AN2 - MIC1 - TCL2 - delta J - CAT - MIC4 - D11S9 - D11S14 - ACP2 - (D11S33, 14L) - CEN. We have used the deletion map to show the distribution on 11p of two centromeric repetitive elements and the low-order interspersed repeat A36Fc. Finally, we provide evidence for an allelic segregation event in the hamster genome that underlies the stability of chromosome 11 in J1. The deletion map provides a basis to position hereditary disease loci on 11p, to distinguish the pattern of recessive mutations in different forms of cancer and, since many of these genes have been mapped in other mammalian species, to study the evolution of a conserved syntenic group.
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PMID:A fine-structure deletion map of human chromosome 11p: analysis of J1 series hybrids. 259 51

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, we performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.
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PMID:Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns. 283 95

The long terminal repeats (LTRs) of retroviruses contain sequences necessary for the initiation and termination of retroviral transcription. These sequences include promoter elements, transcriptional termination signals and transcriptional enhancer elements. The enhancer elements of Moloney murine leukaemia virus (M-MuLV) are localized in a tandemly repeated region (approximately 75 base pairs (bp) long), which lies 5' to the CAT and TATA promoter elements in the U3 region of the LTR (see Fig. 1). We have shown that the tandem repeats are required both for LTR promoter activity, as measured by transient expression assays, and for biological activity, as measured by production of infectious virus. Furthermore, they can be replaced by transcriptional enhancers from the F101 host-range mutant of polyoma virus without loss of function. We report here that the addition of the polyoma (PyF101) enhancers to the M-MuLV LTRs (either with or without the M-MuLV tandem repeats) results in complete loss of viral leukaemogenicity, even though the virus can replicate to high titres in tissue culture fibroblasts and can establish infection in animals.
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PMID:Suppression of leukaemia virus pathogenicity by polyoma virus enhancers. 298 5

Promoter function for gene expression of the long terminal repeat (LTR) of human T-cell leukemia virus type I (HTLV-I) was studied by constructing plasmids containing the LTR sequence. The gene encoding chloramphenicol acetyltransferase (CATase) was linked to an HTLV-I LTR sequence (pLTR-CAT) by replacing the simian virus 40 promoter in plasmid pSV2-CAT with the LTR sequence. The transient CATase activities of cells transfected with the plasmids were compared. The results are summarized as follows: The HTLV LTR was active even in an epithelial cell line, with efficiency similar to that of the simian virus 40 promoter. pLTR-CAT expressed high CATase activity, 40-200 times that expressed by pSV2-CAT, in HTLV-I-infected T-cell lines, such as the human cell lines MT-2 and HUT-102, or in HTLV-I-infected rat cell lines. This enhanced activity of the LTR seems to be associated with HTLV gene expression, since only low activity of pLTR-CAT was observed in the HTLV-infected cell line MT-1, in which only a small percent of cells express viral antigens. In HTLV-infected rat cell lines, the pX-encoded protein p40x was the only viral protein detected. Thus, we suggest that p40x is the factor associated directly or indirectly with the enhanced activity of the LTR.
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PMID:Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor. 298 9

Human T-cell leukemia virus type I has a unique sequence pX and the product p40x was proposed to be a specific trans-acting transcriptional activator of expression of the viral gene. Recently, a second pX protein p27x-III in addition to p40x was identified; these two proteins are encoded by overlapping frames III and IV (x-lor). For determination of which product is the trans-acting activator, site-directed mutations were introduced into the pX sequence which was placed under the metallothionein promoter. On cotransfection with pLTR-CAT (a plasmid containing the LTR of HTLV-I and chloramphenicol acetyltransferase gene), only the mutations that affected p40x expression inactivated the transcriptional activation from the LTR.
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PMID:The p40x of human T-cell leukemia virus type I is a trans-acting activator of viral gene transcription. 300 3

Human T-cell leukemia virus type I has a unique sequence, pX, between the env gene and the 3'LTR (long terminal repeat). This sequence codes for p40x, which was proposed to trans-activate transcription from the LTR. Recently, we identified novel pX proteins coded by frame III, which mostly overlaps frame IV (x-lor, coding for p40x), in a region also overlapped by frame II. To determine which product is responsible for the trans-acting function, we constructed an active provirus clone, pMTPX, that contained a genomic fragment of the env, pX and 3'LTR, and introduced site-directed mutations into the active site. The effects of various deletions and point mutations that distinguished each of the overlapping open reading frames (ORFs), II, III and IV, on trans-activation of pLTR-CAT were treated by co-transfection assays. The results showed that only mutations which affected p40x expression resulted in loss of activity for transcriptional activation. These findings clearly indicate that p40x coded by frame IV is responsible for the transcriptional activation of the LTR. This conclusion was confirmed by studies on expression of cDNA of pX mRNA.
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PMID:Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. 301 13


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