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)

Human T-cell leukemia virus type I (HTLV-I) encodes a trans-activator protein p40x which positively regulates transcription of the viral RNA as well as interleukin-2 and its receptor genes. We placed a cDNA coding for p40x in baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) expression vectors. Infection of BmN cells derived from an insect, B. mori (silkworm), with a recombinant virus led to the production of soluble p40x. The biological activity of the recombinant p40x was demonstrated by introducing the protein into intact NIH 3T3 cells that had been selected for genomic integration of HTLV-I LTR connected with the CAT gene. Immunocytochemical and cell fractionation analyses showed the localization of p40x in both the cytoplasmic and nuclear fractions of BmN cells. Analyses of 32P-labeled proteins of BmN cells by cell fractionation and subsequent immunoprecipitation revealed that the p40x present in each subcellular fraction was phosphorylated. The post-translational modification was inhibited by the addition of a protein kinase inhibitor K252a during the metabolic labeling of BmN cells. Phosphoamino acid analysis indicated that the phosphorylation occurred on serine residues of p40x.
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PMID:Evidence for phosphorylation of trans-activator p40x of human T-cell leukemia virus type I produced in insect cells with a baculovirus expression vector. 305 77

Several human cells were investigated for their ability to degrade tryptophan and to synthesize neopterin upon induction by interferon-gamma (500 units/ml for 48 h). Concentrations of tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, 7,8-dihydroneopterin and neopterin were assessed in the culture supernatants by HPLC. Fibroblasts, A-22 arachnoidea, HK-2351 scalp, T-2346 meningeom and HeLa cervical carcinoma cells but not HL-60 promyelocytic leukaemia cells were found to degrade tryptophan upon induction by interferon-gamma. Tryptophan is converted to kynurenine by fibroblasts, A-22 arachnoidea and HK-2351 scalp cells and to kynurenine and anthranilic acid by HeLa cervical carcinoma and T-2346 meningeom cells. Kynurenine and anthranilic acid always make up more than 82% of the tryptophan degraded. None of these cells synthesizes 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 7,8-dihydroneopterin or neopterin. Human macrophages form 3-hydroxyanthranilic acid and neopterin, but not 3-hydroxykynurenine, beside kynurenine and anthranilic acid upon activation by interferon-gamma. These data indicate that several human cells can be induced by interferon-gamma to degrade tryptophan. The interferon-gamma induced synthesis of 3-hydroxyanthranilic acid and neopterin, however, appears to be restricted to human macrophages. A hypothesis explaining these findings is presented.
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PMID:Interferon-gamma-induced degradation of tryptophan by human cells in vitro. 312 84

The structure of a presumptive DNA intermediate in the integration of retroviral DNA was studied in a cell-free reaction with exogenously added target DNA. The product made by viral core particles of Moloney murine leukemia virus (Mo-MLV) containing linear viral DNA has a structure consistent with an integration mechanism similar to that observed during bacteriophage Mu transposition. In this intermediate, the 3' ends of the LTR sequences are joined to the target DNA, while the 5' ends of the viral DNA remain unjoined. The 5' ends of the LTR sequences in the intermediate are exactly the same as those found in the unintegrated linear double-stranded viral DNA. This result demonstrates that the linear form of Mo-MLV DNA can integrate directly without prior circularization.
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PMID:Retroviral DNA integration: structure of an integration intermediate. 340 25

We describe here an infectious eucaryotic expression vector derived from Moloney Murine Leukemia (Mo-MuLV) provirus and recombined in plasmid pBR 322, for the expression of eucaryotic genes. Upstream of the cloning sites lie the 5' LTR and 700 bp of the gag sequences containing the splicing and encapsidation signals. Downstream of the cloning sites are situated the env gene and the 3' LTR containing the polyadenylation signal. So as to test the potential use of this vector, Herpes Simplex TK gene and E. Coli NeoR genes were cloned in the same transcriptional polarity as the viral LTRs. When DNA from the recombinant plasmid was transfected into mouse, rat, or human cell cultures, high yields of TK+ or NeoR colonies were obtained. Recombinant plasmids constructed with TK or NeoR genes in the opposite polarity failed to produce drug resistant colonies. Cotransfection with DNA of the Mo-MuLV competent helper provirus led to the rescue of chimeric virus capable of transmitting drug resistance.
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PMID:[Construction of an infectious retroviral vector for the expression of eucaryotic genes]. 392 76

A malignant cell line (clone S1) isolated after co-transfection of normal NIH3T3 DNA and Moloney leukemia virus long terminal repeat (Mo-LTR) sequences has previously been described to contain an activated c-raf oncogene. Here, we report the isolation by molecular cloning and the structural analysis of the LTR-activated c-raf gene. As shown by Southern blot and nucleotide sequence analyses, the transfected Mo-LTR sequences integrated into the 5th intron of the endogenous c-raf proto-oncogene. This intragenic LTR insertion led to the expression of high levels of LTR-U5-c-raf hybrid transcripts indicating an initiation of transcription from the Mo-LTR promoter. Transcriptional activation of c-raf is accompanied by the synthesis of large amounts of cytoplasmic c-raf protein. Immunoblot analysis suggests that the proteins encoded by the LTR-activated c-raf gene are truncated compared with the normal c-raf gene product(s). Our results indicate a promoter insertion mechanism of c-raf activation.
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PMID:Integration of transfected LTR sequences into the c-raf proto-oncogene: activation by promoter insertion. 400 4

We studied the genomic structure of human T-cell leukemia virus (HTLV) in the HTLV producer cell line MT-2. Southern blotting revealed that at least eight HTLV proviruses were integrated in the chromosomes of MT-2 cells. The genomic structure of these proviruses was analyzed using fragments of cloned HTLV that were specific to gag, pol, env, pXs and U3R genes as probes. We have identified a complete genome of HTLV in MT-2 (non-defective type). However, seven of the eight proviruses had defective genomes. Provirus T2-a contains only the U3R (LTR) of HTLV and T2-b corresponds to the non-defective genome. T2-c possesses only a portion of env, and pXs and U3R. T2-d consists of gag, pol, part of env and U3R. On the other hand, T2-e, f, g and h consist of gag, pXs and U3R. Northern blotting experiments with mRNA from MT-2 cells supported the evidence of amplification of the gag-pXs gene of HTLV. 26S mRNA is considered to be a subgenomic species of 35S RNA. 32S mRNA may represent the T2-d provirus which lacks a portion of env and pXs, while 20S mRNA was a subgenomic species. The gag-pXs gene may correspond to 24S mRNA, the amount which was amplified in MT-2 cells.
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PMID:Genomic structure of HTLV (human T-cell leukemia virus): detection of defective genome and its amplification in MT-2 cells. 608 18

Human T-cell leukemia virus (HTLV) is a family of related human T-lymphotropic retroviruses closely linked with certain human T-cell malignancies and associated with many cases of acquired immunodeficiency syndrome (AIDS). We isolated and molecularly cloned HTLV from patients with both types of clinical disorders and found by restriction endonuclease mapping and core and envelope protein analysis that at least two evolutionarily divergent viral subgroups exist, HTLV-I and HTLV-II. Previous studies have failed to detect significant nucleotide sequence homology between HTLV-I and HTLV-II even though these different members of the HTLV family share certain biologic properties such as T-cell tropism and transformation. To further test these viruses for conserved regions in their genomes, we examined hybridization between HTLV-I and HTLV-II by using Southern blotting and heteroduplex mapping at different melting points. These two techniques produced similar results, showing that HTLV-I and HTLV-II proviruses have, in fact, strongly conserved nucleotide sequences in the pX region and lesser although still substantial homology in the LTR, gag, pol, and env regions. These data provide experimental evidence that HTLV-II, like HTLV-I, contains pX sequences. Although the function of pX is unknown, its conservation in evolutionarily divergent human T-lymphotropic viruses implies a biologically important function. It is possible, but unproven, that pX could encode proteins involved in T-cell tropism, cell transformation, immune suppression, or other biologic actions characteristic of the HTLV family.
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PMID:Genomes of evolutionarily divergent members of the human T-cell leukemia virus family (HTLV-I and HTLV-II) are highly conserved, especially in pX. 608 32

Eight recombinant DNA clones of endogenous murine leukemia virus (MuLV)-related DNA sequences have been isolated from a lambdaphage genomic library of Balb/c mouse DNA. Each clone contains LTR (long terminal repeat) and gag-related sequences, as well as 5' cellular DNA sequences. The virus-related sequences in each clone show an organization similar to that of integrated proviruses; those clones with the greatest length of MuLV-related sequences also contain pol and env gene-related sequences. One clone appears to contain an intact endogenous provirus. Unique cellular DNA segments from three of these clones were subcloned and used as specific "integration site" hybridization probes. Restriction fragment-length polymorphisms (RFLPs) were observed for these integration sites in the DNA of a number of different inbred mouse strains. One provirus-containing fragment was observed only in Balb/c mice while two others were observed in some but not all of the inbred mouse strains tested. Further restriction enzyme mapping of these three loci in the genomic DNA of Balb/c and C3H/HeJ or C57BL/6 mice indicated that the observed RFLPs were due to the presence of proviral DNA sequences in the Balb/c strain at these three integration sites which were lacking in the other mouse strains. The strain distribution of these three provirus insertions suggests that the BE 1 and 7 proviruses were widely, although not universally, present among the progenitors of modern inbred mouse strains, while the BE 16 provirus may be a recent addition to the genome of Balb/c mice.
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PMID:Molecular clones of endogenous murine leukemia virus-related DNA sequences from Balb/c mice: characterization of integration sites. 609 54

Lymphoid cell lines were established from five different species of monkeys which were positive in antibodies cross-reactive with human T-cell leukemia virus type I (HTLV-I) and were shown to contain provirus sequences homologous to HTLV-I. Gene-specific probes of HTLV-I, gag, pol, env, pX, and LTR, hybridized efficiently with monkey DNAs from these cell lines under stringent conditions, indicating that the proviruses are very similar to HTLV-I along with whole viral genomes. However, the preliminary restriction mapping turned out the difference between simian retroviruses and HTLV-I and also among simian retroviruses. These findings suggest a common ancestor of simian and human retroviruses, but exclude the recent interspecies transmission between monkeys and humans.
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PMID:Detection and characterization of simian retroviruses homologous to human T-cell leukemia virus type I. 609 74

Human T-cell leukemia virus (HTLV) is associated with adult T-cell leukemia (ATL). We have examined the state of the HTLV provirus in the leukemic cells of ATL patients, and found that all the circulating leukemic cells of ATL proliferated monoclonally with one or more proviral integrations. Unexpectedly, we observed a high incidence of multiple integration of the provirus that also revealed a clonality and therefore occurred prior to the clonal origin of the ATL cells. Several ATL patients contained defective proviruses in fresh leukemic cells. These defective proviruses varied with respect to the deleted portions of the HTLV genome when a full genome of the HTLV provirus was present in the ATL tumor cells. In contrast, ATL cells harboring only a defective provirus invariably retained a common sequence of env-pX-LTR. This is consistent with a model that implies that the preserved env-pX-LTR region of HTLV must have played an important role(s) at a certain stage in ATL leukemogenesis after proviral integration. This is the first indication that the whole HTLV genome is not necessarily required to initiate or maintain the monoclonal proliferation of ATL leukemic cells in patients.
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PMID:Defective human T-cell leukemia virus in adult T-cell leukemia patients. 610 May 61


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