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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncogene product from the avian reticuloendotheliosis virus strain T, v-Rel, is a member of the Rel/ NF-kappa B family of transcription factors. The mechanism by which v-Rel induces oncogenic transformation remains unclear. Several attempts to transform mammalian cells with v-Rel have failed, suggesting that v-Rel transformation may be a species-specific event. However, here we demonstrate that v-Rel, but not a truncated c-Rel, expressed under the control of the lck promoter, efficiently induced malignancies in transgenic mice. Most of the animals died before 10 months of age and developed immature, multicentric aggressive T-cell leukemia/lymphomas. Most tumors contain CD4+CD8+ cells or CD4-CD8+ cells, which have an immature rather than a mature peripheral phenotype. No tumor development was observed in control littermates and transgenic mice expressing a truncated form of c-Rel. Tumor formation was correlated with the presence of constitutive p50/v-Rel DNA binding activity and overexpression of several kappa B-regulated genes in v-rel transgenic thymocytes. However, v-Rel is also transforming in transgenic thymocytes lacking p50, indicating that p50/v-Rel heterodimer formation is not essential for the transforming activity of v-Rel. The transforming activity of v-Rel in p50 null mice has been identified as v-Rel/v-Rel homodimers. Since tumors represent immature T-lymphocytes, constitutive v-Rel expression appears to be leukemogenic at earlier stages of T-cell development. These v-Rel mice should aid in the study of lymphoma development, T-cell development and NF-kappa B regulation.
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PMID:The v-rel oncogene promotes malignant T-cell leukemia/lymphoma in transgenic mice. 867 Aug 67

Diseases caused by lymphoid leukosis virus (LLV), a retrovirus, take a long time after infection to develop and have a wide variety of pathological manifestations. This long latent period is characteristic of 'persistent virus infections'. Disease produced by LLV infection and its underlying mechanisms is compared with 'persistent' infections caused by other retroviruses in birds and mammals of veterinary importance. The diseases considered for comparison are those caused by reticuloendotheliosis, feline leukaemia, bovine leukosis and equine infectious anaemia viruses. There are significant changes in the immunological status in all diseases caused by these viruses. LLV infections follow this trend with, in manifestations of neoplastic disease, a perturbation of the normal switch that occurs from IgM to IgG synthesis. There are also indications of other immunological disturbances. Factors other than immunological disturbances may contribute to the length of time after infection required for the many forms of LLV infection to appear. Such additional factors may include the operation of 'biological clocks', such as the arrival of sexual maturity, and also the very nature of retroviruses. These factors, like the immunological changes, play major roles in the maintenance and progression of persistent retrovirus infections.
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PMID:Lymphoid leukosis viruses, their recognition as 'persistent' viruses and comparisons with certain other retroviruses of veterinary importance. 869 4

v-Rel is a transforming protein of the reticuloendotheliosis virus, and is a transcription factor regulating various cellular genes. We found that v-Rel activates the promoter of the proto-oncogene c-jun in a transient transfection assay system. Moreover, the expression of endogenous c-jun was augmented in cells expressing exogenous v-Rel, but not c-Rel. The transcriptional activities of v-Rel to the tested promoters containing the kB-site are lower than that of c-Rel, but that to the c-jun promoter was much higher than that of c-Rel. The N-terminal DNA binding domain of v-Rel, which is responsible for its high transforming activity of v-Rel was also responsible for the high transcriptional activity to the c-jun promoter. Thus, the activity of v-Rel upon the c-jun promoter correlates well with its transforming ability. Since c-Jun plays pivotal roles on cell proliferation in various types of cells, the activation of c-jun expression by v-Rel may be an essential step for the oncogenic transformation caused by v-Rel.
Leukemia 1997 Apr
PMID:v-Rel activates the proto-oncogene c-Jun promoter: a correlation with its transforming activity. 920 5

The murine leukemia virus (MLV)-related type C viruses constitute a major class of retroviruses that includes numerous endogenous and exogenous mammalian viruses and the related avian spleen necrosis virus (SNV). The MLV-related viruses possess a long and multifunctional 5' untranslated leader involved in key steps of the viral life cycle--splicing, translation, RNA dimerization, encapsidation, and reverse transcription. Recent studies have shown that the 5' leader of Friend murine leukemia virus and Moloney murine leukemia virus can direct cap independent translation of gag precursor proteins (Berlioz et al., 1995; Vagner et al., 1995b). These data, together with structural homology studies (Koning et al., 1992), prompted us to undertake a search for new internal ribosome entry segment (IRES) of retroviral origin. Here we describe an IRES element within the 5' leader of avian reticuloendotheliosis virus type A (REV-A) genomic RNA. Data show that the REV-A 5' IRES element maps downstream of the packaging/dimerization (E/DLS) sequence (Watanabe and Temin, 1982; Darlix et al., 1992) and the minimal IRES sequence appears to be within a 129 nt fragment (nucleotides 452-580) of the 5' leader, immediately upstream of the gag AUG codon. The REV-A IRES has been successfully utilized in the construction of novel high titer MLV-based retroviral vectors, containing one or more IRES elements of retroviral origin. These retroviral constructs, which represent a starting point for the design of novel vectors suitable for gene therapy, are also of interest as a model system of internal translation initiation and its possible regulation during development, cancer, or virus infection.
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PMID:Characterization of an internal ribosomal entry segment within the 5' leader of avian reticuloendotheliosis virus type A RNA and development of novel MLV-REV-based retroviral vectors. 938 52

Three species of avian retrovirus cause disease in poultry: the avian leukosis/sarcoma virus (ALSV), reticuloendotheliosis virus (REV), and lymphoproliferative disease virus (LPDV) of turkeys. The ALSV can be classified as slowly transforming viruses, which lack a viral oncogene, and acutely transforming viruses, which possess a viral oncogene. Slowly transforming viruses induce late onset leukoses of the B cell lymphoid, erythroid, and myeloid cell lineages, and other tumors, by viral promoter insertion into the genome of a host cell and activation of a cellular protooncogene. The various acutely transforming leukemia and sarcoma viruses induce leukotic or other tumors rapidly and carry one or anther (sometimes two) viral oncogenes, of which some 15 have been identified. The ALSV fall into six envelope subgroups, A through E, and the recently recognized J subgroup, which induces myeloid leukosis. With the exception of Subgroup E viruses, these viruses spread vertically and horizontally as infectious virions, and are termed exogenous viruses. Subgroup E viruses are usually spread genetically as DNA proviruses (often defective) in host germ cell genome, and are termed endogenous viruses. Several other families of endogenous viruses also exist, one of which, endogenous avian retrovirus (EAV), is related to Subgroup J ALV. Exogenous viruses, and sometimes endogenous viruses, can have detrimental effects on commercially important production traits. Exogenous viruses are currently controlled by virus eradication schemes. Reticuloendotheliosis virus, which lacks a viral oncogene, causes chronic B cell and T-cell lymphomas in chickens, and also chronic lymphomas in turkeys and other species of birds. An acutely transforming variant of REV, Strain T, carries a viral oncogene, and induces reticuloendotheliosis within a few days. In chickens and turkeys, REV spreads vertically and horizontally. No commercial control schemes are operated. In turkeys, LPDV infection has occurred in several countries, where it caused a lymphoproliferative disease of uncertain nature.
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PMID:Retrovirus-induced disease in poultry. 970 91

In addition to their role in reverse transcription, the R-region sequences of some retroviruses affect viral transcription. The first 28 nucleotides of the R region within the long terminal repeat (LTR) of the murine type C retrovirus SL3 were predicted to form a stem-loop structure. We tested whether this structure affected the transcriptional activity of the viral LTR. Mutations that altered either side of the stem and thus disrupted base pairing were generated. These decreased the level of expression of a reporter gene under the control of viral LTR sequences about 5-fold in transient expression assays and 10-fold in cells stably transformed with the LTR-reporter plasmids. We also generated a compensatory mutant in which both the ascending and descending sides of the stem were mutated such that the nucleotide sequence was different but the predicted secondary structure was maintained. Most of the activity of the wild-type SL3 element was restored in this mutant. Thus, the stem-loop structure was important for the maximum activity of the SL3 LTR. Primer extension analysis indicated that the stem-loop structure affected the levels of cytoplasmic RNA. Nuclear run-on assays indicated that deletion of the R region had a small effect on transcriptional initiation and no effect on RNA polymerase processivity. Thus, the main effect of the R-region element was on one or more steps that occurred after the template was transcribed by RNA polymerase. This finding implied that the main function of the R-region element involved RNA processing. R-region sequences of human immunodeficiency virus type 1 or mouse mammary tumor virus could not replace the SL3 element. R-region sequences from an avian reticuloendotheliosis virus partially substituted for the SL3 sequences. R-region sequences from Moloney murine leukemia virus or feline leukemia virus did function in place of the SL3 element. Thus, the R region element appears to be a general feature of the mammalian type C genus of retroviruses.
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PMID:The secondary structure of the R region of a murine leukemia virus is important for stimulation of long terminal repeat-driven gene expression. 973 16

Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture. In this study, we addressed whether the 5' region of VL30m could replace the 5' leader of MoMLV functionally in a recombinant vector construct. Our data confirm that the putative packaging sequence of VL30 is located within the 5' region (nucleotides 362 to 1149 with respect to the cap structure) and that it can replace the packaging sequence of MoMLV. We also show that VL30m contains an internal ribosome entry segment (IRES) in the 5' region, as do MoMLV, Friend murine leukemia virus, Harvey murine sarcoma virus, and avian reticuloendotheliosis virus type A. Our data show that both the packaging and IRES functions of the 5' region of VL30m RNA can be efficiently used to develop retrotransposon-based vectors.
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PMID:Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors. 1048 90

The 5' leader of Rous sarcoma virus (RSV) genomic RNA and of retroviruses in general is long and contains stable secondary structures that are critical in the early and late steps of virus replication such as RNA dimerization and packaging and in the process of reverse transcription. The initiation of RSV Gag translation has been reported to be 5' cap dependent and controlled by three short open reading frames located in the 380-nucleotide leader upstream of the Gag start codon. Translation of RSV Gag would thus differ from that prevailing in other retroviruses such as murine leukemia virus, reticuloendotheliosis virus type A, and simian immunodeficiency virus, in which an internal ribosome entry segment (IRES) in the 5' end of the genomic RNA directs efficient Gag expression despite stable 5' secondary structures. This prompted us to investigate whether RSV Gag translation might be controlled by an IRES-dependent mechanism. The results show that the 5' leaders of RSV and v-Src RNA exhibit IRES properties, since these viral elements can promote efficient translation of monocistronic RNAs in conditions inhibiting 5' cap-dependent translation. When inserted between two cistrons in a canonical bicistronic construct, both the RSV and v-Src leaders promote expression of the 3' cistron. A genetic analysis of the RSV leader allowed the identification of two nonoverlapping 5' and 3' leader domains with IRES activity. In addition, the v-Src leader was found to contain unique 3' sequences promoting an efficient reinitiation of translation. Taken together, these data lead us to propose a new model for RSV translation.
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PMID:Rous sarcoma virus translation revisited: characterization of an internal ribosome entry segment in the 5' leader of the genomic RNA. 1109 Jan 56

Hairy cell leukaemia, previously known as leukaemic reticuloendotheliosis, is an indolent lymphoproliferative disorder of unknown etiology. It typically affects males, causes marked splenomegaly and moderate enlargement of the liver, whilst lymphadenopathy is inconspicuous. Pancytopenia is characteristic with unusually profound monocytopenia, variable reduction in platelets, and the presence in the peripheral blood and marrow of abnormal small lymphocytes having irregular cytoplasmic margins. Ultrastructure, combined with cytochemistry and flow cytometry, have refined diagnosis. A variant exists between this classical entity and B prolymphocytic leukaemia, where blastic transformation or massive lymph node enlargement are found, and this is of ominous significance. In all these patients with this entity conventional chemotherapy is ineffective and shortens survival. Our previous experience with splenectomy results in excellent clinical control for long periods of time, but without disease eradication. There followed a vogue for the use of interferon but this is limited by high cost and dose-dependent side-effects. Contemporary management centres on the purine analogues, where durable responses are possible with fludarabine and deoxycoformycin, but best with 2'chlorodeoxyadenosine (2-CDA). To document the efficacy of the latter agent, we analysed the outcome in seventeen consecutive patients treated over the last five years. Four were ineligible for analysis, although two had 2-CDA. The other thirteen, managed on a standard seven-day course of 0.1 mg/kg 2-CDA given as a continuous intravenous infusion, all responded promptly. Apart from transient leucopenia complications have been minimal, and oral co-trimoxazole prophylaxis for pneumocystis carinii was maintained during the first one year. In all thirteen there was a rapid return to normal of peripheral blood count and marrow on aspiration and trephine biopsy. Even in the longest follow-up clinical and haematologic remission has been maintained and no patients have required retreatment. One individual has relapsed in the marrow at two years. Despite the relative expense of the agent the excellent treatment outcome and patient acceptability, coupled with its safety, leads to the recommendation that in South Africa - as elsewhere in the world - this be regarded as the first line of treatment.
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PMID:Malignancy: 2'-Chlorodeoxyadenosine Effectively Induces Complete Remission in Hairy Cell Leukaemia. 1139 82

The 5' untranslated region (UTR) of retroviruses contain structured replication motifs that impose barriers to efficient ribosome scanning. Two RNA structural motifs that facilitate efficient translation initiation despite a complex 5' UTR are internal ribosome entry site (IRES) and 5' proximal post-transcriptional control element (PCE). Here, stringent RNA and protein analyses determined the 5' UTR of spleen necrosis virus (SNV), reticuloendotheliosis virus A (REV-A) and human T-cell leukemia virus type 1 (HTLV-1) exhibit PCE activity, but not IRES activity. Assessment of SNV translation initiation in the natural context of the provirus determined that SNV is reliant on a cap-dependent initiation mechanism. Experiments with siRNAs identified that REV-A and HTLV-1 PCE modulate post-transcriptional gene expression through interaction with host RNA helicase A (RHA). Analysis of hybrid SNV/HTLV-1 proviruses determined SNV PCE facilitates Rex/Rex responsive element-independent Gag production and interaction with RHA is necessary. Ribosomal profile analyses determined that RHA is necessary for polysome association of HTLV-1 gag and provide direct evidence that RHA is necessary for efficient HTLV-1 replication. We conclude that PCE/RHA is an important translation regulatory axis of multiple lymphotropic retroviruses. We speculate divergent retroviruses have evolved a convergent RNA-protein interaction to modulate translation of their highly structured mRNA.
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PMID:RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1. 1742 38


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