Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fresh and cultured leukemia cells from an adult T-cell leukemia (ATL) patient which possessed gag and env gene defective human T-cell leukemia virus type I (HTLV-I) provirus genome were molecularly analyzed. Cells from both fresh and the established cell line, named KB-1 showed identical surface markers of helper T cells, expressed the interleukin 2 (IL-2) receptor and had an identical defective HTLV-I provirus genome with deletions of the gag and env genes involving pX gene exon 2. The KB-1 cells grew vigorously in vitro, even in the absence of IL-2 and the culture supernatant of KB-1 contained a large amount of IL-2. Neither pX mRNA nor p40(TAX) protein was detected in the KB-1 cells. The collective evidence suggests that the pX gene was not functioning in this particular ATL case. The biological function of the HTLV-I genes, especially the pX gene is discussed in relation to the early and late leukemogenesis of ATL.
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PMID:Molecular analysis of a HTLV-IpX defective human adult T-cell leukemia. 140 24

Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.
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PMID:Lack of evidence for the involvement of type-C and type-B retroviruses in radiation leukemogenesis of NFS mice. 169 Apr 35

As an approach to evaluating the contribution of classes of endogenous viral sequences to leukemogenesis, a genomic library was prepared from the highly tumorigenic AKR SL12.3 cell line and screened for env-containing proviruses. An extensive battery of virus-derived probes and specific oligonucleotide probes were used to segregate 83 positive clones into related groups. The nonecotropic endogenous retroviruses were identified as members of the polytropic, modified polytropic, or xenotropic groups. At least three unique xenotropic proviruses were detected that differed from the published xenotropic sequence within a variable region of the 5' portion of env. Changes among the xenotropic proviruses included relative insertions and/or deletions that maintain an open reading frame and hence the potential to encode viable envelope gene products. Several recombinant viruses were also detected. Recombination was not random and primarily involved the formation of mink cell focus-inducing class I retroviruses via recombination between polytropic elements and ecotropic virus. One other recombinant was detected which contained ecotropic virus sequences in the 5' region encoding p15 of an otherwise xenotropic provirus. An interesting observation was the finding that certain clones contained more than one provirus within the average 20-kb cloned insert. This would not be expected if integration were totally random. The de novo recombinant proviruses identified here provide a series of potential candidates to be evaluated for their contribution to the tumorigencity of the SL12.3 cell line.
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PMID:Characterization of endogenous and recombinant proviral elements of a highly tumorigenic AKR cell line. 187 Jan 92

Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfection experiments showed growth stimulation of NIH 3T3 cells--growing beyond the saturation density and growing in soft agar. Since the pX sequence is known to encode three proteins, Tax, Rex, and p21x, the biological activity of each pX gene was examined separately. The growth-stimulating activity was induced only by the tax gene in NIH 3T3 cells and Rat-1 cells. Furthermore, the tax gene induced tumorigenicity in nude mice when introduced into Rat-1 cells. Thus, a transcriptional transactivator gene of HTLV-I, tax, is clearly identified as a viral oncogene without a cellular homolog. The transforming activity of tax, possibly via a transcriptional deregulation of cell growth control, may play an important role in leukemogenesis of ATL in addition to its aberrant stimulation of the interleukin 2 system.
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PMID:Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro. 230 May 70

Spontaneous AKR leukemias express murine leukemia virus (MuLV) gag and env gene-encoded structural proteins on their cell surface. Cytotoxic T lymphocytes (CTL) induced in AKR mice by syngeneic leukemia 369 which expressed high amounts of H-2 antigens recognized viral gag polyproteins in association with H-2K antigens as target antigens. H-2K-negative leukemias were resistant to lysis by AKR/Gross MuLV-specific CTL and did not induce a cellular immune response. However, they became susceptible after stimulation with interferon. H-2K-positive leukemias induced CTL which were cytotoxic for 369 cells. However, the majority of H-2K-positive leukemias was not lysed by CTL induced by autologous immunization. These leukemias were also resistant to lysis by anti-369 CTL, but could restimulate AKR/Gross-specific CTL in vitro, and were susceptible to lysis by H-2Kk-restricted CTL against AKR minor histocompatibility antigens. Thus, there could be specific defects of the H-2Kk antigens of these tumors. However, there were also qualitative and quantitative differences in antigenic determinants of the gag target antigens in these leukemias. Therefore, in addition to quantitative reduction of the H-2K restriction elements, qualitative alterations of H-2 antigens or of the viral target antigens may impair T cell cytotoxicity and thus influence leukemogenesis of AKR spontaneous leukemia.
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PMID:Resistance to cellular immune response in AKR leukemias. 242 71

Inbred strains of mice contain in the genome 40-60 endogenous proviruses related to murine leukemia virus. To assess the genetic and pathogenic consequences of these to the host, we have developed a strategy to distinguish among the three different host-range subgroups--xenotropic, polytropic and modified polytropic--by using oligonucleotide probes specific for a polymorphic region in env. Each of these proteins detects a relatively small number of bands in a Southern blot, thus permitting us to enumerate all individual proviruses of this group. Using this approach, we have determined the distribution of different proviruses among inbred and recombinant inbred (RI) strains congenic or coisogenic for specific mutants. Using the RI results, we have been able to place over 100 proviruses on the mouse genetic map. A number of these are closely linked to well-characterized mutations, and we have been able to establish that at least one mutation, hr (hairless), was caused by a proviral insertion. If the other close linkages also prove to reflect causality, we estimate that up to 5% of recessive mutations in the mouse might be caused by insertion of proviruses of this group. Using a similar probe strategy, we have followed the evolution of murine leukemia viruses during spontaneous leukemogenesis in AKR mice. We have found that the final leukemogenic (MCF) virus is a recombinant of three different endogenous parents; an ecotropic virus, a polytropic virus that directs the gp70 region of env, and a xenotropic virus (identified as the inducible element Bxv-1) that directs the LTR. In addition to the recombinations, all such viruses also have a reduplication of the enhancer region of the LTR, compared to the endogenous parent. MCF viruses are created by these three genetic changes, which occur in a reproducible fashion and appear in the thymus between 10 and 14 weeks of age.
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PMID:Genetics of endogenous murine leukemia viruses. 255 92

Friend virus clearly provides an important model for understanding the molecular biology of cancer. Moreover, the most important aspects of the erythroleukemia can be caused by a single SFFV infection in the absence of any helper virus. The SFFV env gene encodes a membrane glycoprotein, gp55. This glycoprotein, when expressed on erythroblast surfaces, causes a constitutive mitogenesis. However, SFFV infections only rarely increase the cell's self-renewal capability or abrogate its commitment to differentiate. Therefore, the consequence of infection is initially a polyclonal erythroblastosis. This polyclonal proliferation usually leads to cell differentiation and to recovery unless helper virus is present to cause continuing infection of new erythroblasts. Extremely rare SFFV proviral integrations, however, result in abrogation of the cell's commitment to differentiate and in the concomitant acquisition of cell immortality. These immortalizing proviral integrations occur at only a small number of sites in the mouse genome. Therefore, the mitogenic and immortalizing stages of erythroleukemia are now known to be caused by discrete genetic events--the first involving the SFFV env gene and the second involving the rare proviral integration sites. In early investigations of Friend virus, the first stage always preceded the second stage by at least several weeks. Now it is known that this delay in onset of the second stage is caused solely by statistics. Every SFFV-infected erythroblast is mitogenically activated, yet only rarely does the SFFV proviral integration produce immortality. Both steps in leukemogenesis can be caused simultaneously in an erythroblast by a rare single SFFV proviral integration. There has been an explosion of interest in retroviral env gene-mediated pathogenesis. Such pathogenesis has been recently associated with most of the naturally transmitted retroviral diseases including AIDS. Such pathogenesis involves in different viruses immunosuppression, anemia, neuropathy, and leukemia (Mathes et al. 1978; Simon et al. 1984, 1987; Weiss et al. 1985; Lifson et al. 1986; Riedel et al. 1986; Sitbon et al. 1986; Sodroski et al. 1986; Mitani et al. 1987; Schmidt et al. 1987; Klase et al. 1988; Overbaugh et al. 1988a, b). The shuffling and dynamic env gene rearrangements that have been associated with murine retroviral leukemogenesis have also now been seen in FeLV-FAIDS and HIV (Fisher et al. 1988; Overbaugh et al. 1 t88b; Saag et al. 1988; Tersmette et al. 1988). Friend virus provides an important established example of such env gene pathogenesis. Although we still do not understand precisely how gp55 causes erythroblast mitosis, workers in this field have discovered important clues that may lead to answers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of Friend viral erythroleukemia. 268 47

3-Methylcholanthrene-induced T-cell thymic lymphomas in RF mice were examined for involvement of murine leukemia virus (MuLV)-related sequences in leukemogenesis. Both the expression of MuLV-related RNA species and the organization of endogenous MuLV proviral DNA were analyzed. Of 27 primary tumors examined, only 5 exhibited elevated MuLV-related RNA species homologous to xenotropic specific env DNA. None of these RNA species hybridized with ecotropic p15E DNA sequences. Only two of these five tumors contained MuLV-like RNA species that hybridized with ecotropic MuLV long terminal repeat sequences, despite the probe's ability to detect both ecotropic MuLV and mink cell focus-inducing viral RNA. No muLV resembling mink cell focus-inducing virus whose expression could be correlated with lymphomagenesis was detected in either preleukemic thymocytes, primary 3-methylcholanthrene-induced thymic tumors, tumors passaged in vivo, or cell lines derived from tumors. Restriction endonuclease analysis of DNA from both primary tumors and cell lines failed to reveal either proviral DNA with recombinant env genes or rearrangement of endogenous MuLV proviruses. Therefore, chemically induced lymphomagenesis in RF mice appears different from the spontaneous lymphomagenic process in AKR mice with respect to the involvement of endogenous MuLV sequences.
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PMID:Comparison of endogenous murine leukemia virus proviral organization and RNA expression in 3-methylcholanthrene-induced and spontaneous thymic lymphomas in RF and AKR mice. 298 67

Endogenous murine leukemia virus (MuLV) proviral copies were analyzed in thymomas induced in normal BALB/c (Fv-1b) and in Fv-1n congenic mice by X-irradiation. Both strains of mice developed leukemia with similar kinetics, indicating that N-tropism of endogenous MuLV was not a rate-limiting factor in development of disease. Southern blot analysis, using a probe specific for ecotropic virus and for ecotropic-specific sequences retained in pathogenic, env-recombinant viruses, showed that the majority of radiation leukemias lacked newly acquired, clonally integrated, proviruses. This was in contrast to virus-induced leukemias, which routinely exhibited several new proviral integration sites. When an internal proviral DNA restriction fragment was monitored, some radiation leukemias showed evidence of nonclonal infection, accounting for more frequent isolation of infectious virus from such leukemias. Differences in expression of T-cell surface antigens were found in X-ray-induced and virus-induced leukemias. All radiation leukemias were TL positive, whereas virus-induced leukemias were primarily negative for TL. Some differences were also found in Lyt-1 and Lyt-2 expression. The data as a whole suggest that, in the majority of cases, radiation leukemogenesis is not initiated by a viral route--that is, the sort of viral mechanism for which exogenous infection by known pathogenic MuLV is the paradigm.
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PMID:A comparative analysis of radiation- and virus-induced leukemias in BALB/c mice. 298 45

A retrovirus highly related to human T-cell leukemia virus type I (HTLV-I) was isolated from a T-cell line established from a seropositive pig-tailed monkey and the provirus genome was molecularly cloned using HTLV-I as a probe. The monkey virus (STLV) had the genomic structure of the LTR-gag-pol-env-pX-LTR. Analysis of the env-pX-LTR region revealed the 90% homology of the nucleotide sequence with that of HTLV-I in each region. This high homology of the sequence indicates that STLV is a member of the HTLV family, but apparently different from HTLV-I. This suggests that the possibility of recent interspecies transmission from monkeys to humans in the endemic area is very small. From its similarity to HTLV, STLV should be useful as an animal model in studies on natural HTLV infection and leukemogenesis of HTLV in humans.
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PMID:Sequence homology of the simian retrovirus genome with human T-cell leukemia virus type I. 299 47


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