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 human T-cell leukemia virus type-1 (HTLV-1) contains a unique pX region, which encodes the gene products p40 chi, p27 chi-III and p21 chi-III. p40 chi is required for transcriptional trans-activation, whereas p27 chi-III and p21 chi-III have no such function. Transfection of pX expression plasmids containing different combinations for the three gene products into cells integrated with HTLV-1 proviruses defective in pX expression revealed that both p40 chi and p27 chi-III are required for expression of the gag protein and accumulation of gag mRNA. These observations suggest that the pX product p40 chi activates transcription and p27 chi-III controls the level of gag mRNA by post-transcriptional modulation.
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PMID:The second pX product p27 chi-III of HTLV-1 is required for gag gene expression. 302 15

We isolated the full length provirus of human T cell leukaemia virus type I (HTLV-I) from MT-2, a lymphoid cell line producing HTLV-I. In three non-lymphoid cell lines (COS7, human osteosarcoma HOS cells, and HeLa) this provirus expressed a trans-acting activity after co-transfection with a recombinant plasmid carrying a bacterial chloramphenicol acetyltransferase gene under the control of a long terminal repeat of HTLV-I provirus. The trans-acting protein p40 was detected by immunoprecipitation in transfected HOS cells. Structural proteins of HTLV-I, the gag and env products, were also formed and processed in the same manner as observed in MT-2 cells. In transfected HeLa cells, the p40 protein was mainly localized in the nucleus, while other structural proteins were detected in the cytoplasm and/or the membrane by indirect immunofluorescence. Syncytium formation was observed in HeLa cells after transfection. These results demonstrated that non-lymphoid cells could produce the major proteins of HTLV-I after DNA transfection of the cloned provirus.
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PMID:Expression of a provirus of human T cell leukaemia virus type I by DNA transfection. 302 87

Human T-cell leukemia virus type I has a unique sequence, pX, between env and the 3' long terminal repeat (LTR). One of its products, p40, activates gene expression directed by the LTR in a trans-acting manner. We have analysed the mechanism of this trans-activation mediated by p40 in human T cells co-transfected with a plasmid expressing p40 using the transient CAT gene expression. We identified two distinct elements in the LTR which are involved in maximum gene expression. The first was present in a 230-bp fragment upstream from TATA box in the U3 region and behaved as a classical enhancer. This region was also shown to be responsible for trans-activation by p40. This element alone together with functional p40 could direct the gene expression at only approximately 10% of the level achieved by the complete LTR and p40. The second element was present within a 300-bp fragment downstream from the RNA start site and profoundly enhanced the gene expression in a way independent from trans-activation mechanism. This enhancement was observed only when the element was located immediately downstream from the RNA start site without orientation preference. These two elements participate independently in the enhancement of gene expression.
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PMID:Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression. 303 89

Human T-cell leukemia/lymphoma virus (HTLV)-carrying cells from various origins were characterized by cell surface markers and expression of HTLV antigens. Eight cell lines named TCL were obtained by transformation of peripheral blood leukocytes (PBL) of healthy donors or HTLV carriers in cocultures with HTLV-producer MT-2 cells. Nine cell lines named ILT were interleukin 2 (IL2)-dependent cell lines cloned from PBL of ATL patients and healthy HTLV-carriers. Tc-Kan9 cell line was also an IL2-dependent cell line clonally established from PBL culture stimulated with autologous TCL cells. Five cell lines named TL were established in vitro directly from PBL of an adult T-cell leukemia (ATL) patient and from ILT cells of an ATL patient and three HTLV-carriers, respectively, to grow autonomously without IL2. All the TCLs, ILTs, TLs and Tc-Kan9 possessed Leu-I antigen, a pan-T-cell marker. Leu3a antigen, a helper/inducer T-cell marker, was expressed on five of eight TCLs and all of the ILTs and TLs. Leu-2a, a cytotoxic/suppressor T-cell marker, was detected only on Tc-Kan9 but not others. Fresh ATL leukemic cells of patients had a helper/inducer T-cell marker. Ia, OKT9 and Tac antigens, markers for activated and differentiated T cells, were strongly expressed on all of the cell lines tested and fresh ATL leukemic cells were weakly positive for these antigens. Expression of HTLV antigens detected by mouse monoclonal antibodies and an ATL-patient serum varied among these cell lines. One TL, two ILTs and most of the fresh ATL leukemic cells did not express HTLV antigens on the cell surface. The other cell lines were all positive for the surface viral antigens. However, molecular species of antigens defined by radioimmunoprecipitation with an ATL-patient serum were not always identical among the cell lines. Molecular weights of polypeptides detectable in most of the cell lines were 62K, 46K, 40K, 24K, 21K and 19K which could never be detected in several control T-cell lines. 68K and 28K polypeptides were frequently detected in MT-2 and TGLs. GIN14, a mouse monoclonal antibody against HTLV core protein (p19) detected not only p19 in various cell lines but also p28, p29, p31 or p40 in certain cell lines tested. B-cell lines named LCL were established and cloned from PBL of two HTLV-carriers by EB-virus-induced transformation and they also expressed HTLV antigens, Ia, OKT9 and Tac antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cell surface phenotypes and expression of viral antigens of various human cell lines carrying human T-cell leukemia virus. 608 3

Preparations of purified Rauscher murine leukemia virus were found to contain an endodeoxyribonuclease after disruption of the virus with nonionic detergents. The enzyme makes single-strand breaks in linear or covalently closed circular phage double-stranded DNA molecules. The enzyme was partially purified by ion-exchange chromatography on DEAE- and carboxymethyl-Sepharose columns followed by electrophoresis in DNA-containing polyacrylamide gels. The enzyme was separated from reverse transcriptase (p80pol), and the final endonuclease preparation contained no detectable reverse transcriptase activity. The DEAE-Sepharose column-purified endonuclease activity contained a polypeptide of about 40,000 Mr that we term p40. Peptide mapping experiments demonstrated that p40 shares methionine-labeled tryptic peptides with Pr200gag-pol and Pr135pol. Six major methionine-labeled tryptic peptides derived from p40 were found in Pr200gag-pol, but only five of these were detected in Pr135pol. The four core proteins (p30, p15, pp12, and p10) and p80pol plus p40 account for most, but not all, of the peptide sequences of Pr200gag-pol. The endonuclease-associated p40 is similar in size and precursor origin to the avian retrovirus-coded endonuclease (p32). In view of these similarities to the avian p32 endonuclease and its association with partially purified Rauscher murine leukemia virus-associated endonuclease preparations, we propose that p40 is the Rauscher murine leukemia virus-coded endonuclease.
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PMID:Endodeoxyribonuclease activity associated with Rauscher murine leukemia virus. 626 Sep 82

The murine AIDS (MAIDS) virus has a unique sequence in the gag p12 region, which could be responsible for MAIDS development. RNA preparations from the spleens of normal uninfected C57BL/6 mice contain a transcript hybridizing with this sequence. Levels of the transcript in the kidney of C57BL/6 mice were higher than in the spleen, liver or thymus. Although BALB/c, NFS, DBA/2 and SL murine strains also contained genomic sequences hybridizing with the MAIDS virus-specific probe, no transcript hybridizing with the probe was detected in these strains of mice. The cDNAs carrying the transcript expressed in C57BL/6 mice were molecularly cloned. The complete nucleotide sequence of the clone indicates that the transcript is one of the endogenous murine leukaemia virus-related sequences containing large deletions from the R and U5 regions of the 5' long terminal repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the N-terminal region of env p15E, and many short deletions in the 3' LTR U3 region. The nucleotide sequence in the gag p12 region of the transcript was closely similar to that of the MAIDS virus, but the amino acid sequence was less similar because of frameshifting, even when translated. As the MAIDS virus was isolated from C57BL/6 mice with radiation-induced leukaemia, this transcript may be the progenitor of the MAIDS virus. To determine whether the gag p12 region of the transcript contains a functional sequence, a recombinant virus was generated by replacing the gag p12 region of a replication-competent BM5eco virus with that of the endogenous transcript. The recombinant virus was replication-competent, and the p12 region of the transcript retained the functional sequence present in the BM5eco virus.
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PMID:Molecular cloning and characterization of a murine AIDS virus-related endogenous transcript expressed in C57BL/6 mice. 751 20

Geldanamycin is an antibiotic that preferentially inhibits G1/S transition and causes G2/M arrest in human leukemia HL-60 cells. With it, we selectively inhibited recombinant Src tyrosine kinase without significantly inhibiting protein kinase A. The perturbation of cell cycling by geldanamycin was accompanied by marked suppression of c-MYC expression. In contrast to this, pRB expression was remarkably enhanced by geldanamycin. In the untreated HL-60 cells, c-MYC was apparently enriched in nuclear matrix preparation, and significant amounts of hyperphosphorylated pRB, p70 and p40 proteins were observed to associated with the nuclear matrix. The amounts of these proteins associated with the nuclear matrix, however, were markedly decreased by treatment with geldanamycin. This finding suggests that the association of c-MYC, hyperphosphorylated pRB, p70 and p40 proteins with the nuclear matrix is essential in cell cycling, especially in G1/S and G2/M progressions, and that this association is a part of signal transduction pathway in Src kinase activation.
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PMID:Inhibition of the association with nuclear matrix of pRB, p70 and p40 proteins along with the specific suppression of c-MYC expression by geldanamycin, an inhibitor of Src tyrosine kinase. 759 47

We investigated the effect of tannic acid, a potent inhibitor of poly(ADP-ribose) glycohydrolase, on human viral gene transcription, by using chloramphenicol acetyl transferase (CAT) assay experiments transfecting Jurkat cells with CAT reporter constructs that contain the promoter region of human immunodeficiency virus (HIV) or of human T-cell leukemia virus type I (HTLV-1). The activity of HIV promoter induced by treatment with 12-O-tetradecanoylphorbol-13-acetate was suppressed by the addition of tannic acid. On the other hand, HTLV-1 promoter activity induced by the p40(tax) expression plasmid was not affected by tannic acid treatment. Deletion analysis of the HIV promoter revealed that a 30-bp element located immediately upstream of NF-kappa B motifs was responsible for the suppressive effect of tannic acid. This was supported by the observations that the negative effect of tannic acid was introduced to tannic acid-non-responsive thymidine kinase promoter by the insertion of this element 5'-upstream of the promoter.
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PMID:Inhibitory effect of tannic acid on human immunodeficiency virus promoter activity induced by 12-O-tetra decanoylphorbol-13-acetate in Jurkat T-cells. 864 19

The combination of immunotherapy with conventional treatments such as radio- and chemotherapy may be necessary to eradicate minimal residual disease. Interleukin 12 (IL-12) is a heterodimeric cytokine composed of two subunits, p40 and p35. Coordinate expression of the IL-12 p40 and p35 genes in several solid tumor models has been found to induce strong and specific antitumor immune responses. In the interest of obtaining high level IL-12 expression in leukemia/lymphoma cells for use as vaccines in cancer immunotherapy, we evaluated three IL-12 retroviral vector designs based on the murine stem cell virus (MSCV) vector which efficiently transduces functional genes into normal hematopoietic cells. MSCVpac-mlL-12 and MIPV-mIL-12 contain an encephalomyocarditis virus internal ribosome entry site for internal translation of bicistronic mRNA transcripts, while MDCVpac-mIL-12 carries an expression cassette in the U3 region of the 3' long terminal repeat. We found that the MSCVpac-mIL-12 vector directed robust expression of both p40 and p35 genes in several murine tumor cell lines of hematopoietic origin, including a T-cell lymphoma, a B-cell lymphoma, and a plasmacytoma/myeloma. In contrast, genomic instability or promoter interference hampered p40 gene expression in cells transduced with the MIPV-mIL-12 and MDCVpac-mIL-12 vectors, respectively. These findings provide the basis for the design of IL-12 retroviral vectors for the treatment of hematologic malignancies in humans.
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PMID:Transmissibility of murine stem cell virus-based retroviral vectors carrying both interleukin-12 cDNAs and a third gene: implications for immune gene therapy. 917 35

Our recent studies using various costimulatory molecules have demonstrated that antitumor effect could be induced by B7- or B70-transduced mouse tumors. To augment antitumor effect in vivo, the combination therapy with a costimulatory gene and a cytokine, interkeukin 12 (IL-12), gene to treat metastatic mouse lung tumor was investigated. We transfected with mouse B7 and/or IL-12 into mouse lung carcinoma 3LL, and three transfectants (IL-12/3LL, B7/3LL and IL-12/B7/3LL) were generated. CTL activity induced by the inoculation of IL-12/B7/3LL was increased about 10-fold compared with parental 3LL inoculation. We then examined the therapeutic efficacy of combination with B7 and IL-12-transduced tumors. Four weeks after 3LL inoculation, lung metastasis was significantly reduced by IL-12/B7/3LL post-inoculation, indicating that potent therapeutic antitumor immunity can be induced by combination with costimulators B7 and IL-12. Recently, it was reported that p40 subunit of IL-12 appeared to be a specific inhibitor for IL-12 heterodimer in vitro. To clarify the biological functions of p40 in vivo, we generated the myoblast transfectants which produced IL-12 p40 alone. Local production of IL-12 p40 from transfectant could suppress allogenic CTL induction and Th1-type antibodies (IgG2a/2b/3) production in vivo. Furthermore, IL-12 p40 producing myoblast are less susceptible to rejection compared with parental myoblast, indicating that IL-12 p40 gene transfer may be useful therapeutically in Th1-mediated transplantation and autoimmune disorders.
Leukemia 1997 Apr
PMID:Immunoregulation by B7 and IL-12 gene transfer. 920 58


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