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

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.
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PMID:Discussion paper: protective immunity in leukemic mice treated with specific "immunogenic" RNA. 106 68

BALB/c mice infected with Rowson-Parr virus, a lymphatic leukemia virus isolated from the Friend complex, undergo a rapid depression of antibody response. Spleen cells from these mice in culture show a similar deficit in the response to stimulation with sheep red cells and inhibit the reactivity of normal splenocytes. In an attempt to reverse this immunosuppression, near normal responses were obtained in vitro from infected splenocytes by increasing antigen dose, by adding E. coli lipopolysaccharide, or, more effectively, by cocultivating with small numbers of unfractionated or T cell-depleted peritoneal exudate cells (PC), whereas other manipulations proved ineffective. PC did not prevent the inhibition of normal splenocytes by infected spleen cells, but exhibited substantial restorative activity in vivo. In similar experiments, the immunosuppression exerted by the entire Friend complex could be reversed by PC in vitro but not in vivo. These results indicate that a functional deficit of macrophages may be partially responsible for the immunological impairment induced by leukemia viruses and suggest rational approaches to evaluate the relevance of this impairment to oncogenesis.
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PMID:Reversal of immunosuppression induced by murine leukemia viruses. 107 70

The presence of endogenous oncornavirus and herpesvirus in guinea pigs has been established. The oncornavirus apparently is present in all guinea pigs but is expressed only under certain conditions. Expression of the latent herpesvirus is generally age and strain dependent as is the development of spontaneous guinea pig leukemia. Following special laboratory manipulation, expression of both virus types was accomplished in vitro. Studies of the role played by these two virus types in the development of neoplastic disease in guinea pigs revealed that, in the presence of the endogenous oncornavirus, a superinfection with herpesvirus led to the development of self-limited lymphoproliferative changes. Together with the studies reported by other investigators, it appears that interaction between the DNA and RNA viruses may play an important role in the natural occurrence of viral oncogenesis. Guinea pigs provide an intriguing animal model for the study of herpesvirus and oncornavirus interaction both in vivo and in vitro.
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PMID:An animal model for DNA-RNA virus interaction based upon virological and histological findings. 125 55

We have identified nucleotide sequences that regulate transcription in both a cell-type-specific and general manner in the long terminal repeat of the MCF13 murine leukemia virus. Besides the enhancer element, we have observed that the region between the enhancer and promoter (DEN) has a profound effect on transcription in different cell types. This effect, however, was dependent on the copy number of enhancer repeats and was detectable in the presence of a single repeat. When two enhancer repeats were present, the effect of DEN on transcription was abrogated except in T cells. DEN also makes a significant contribution to the leukemogenic property of the MCF13 retrovirus. Its deletion from the MCF13 virus dramatically reduced the incidence of thymic lymphoma and increased the latency of disease in comparison with the wild-type virus. This effect was most marked when one rather than two enhancer repeats was present in the mutant viruses. We also observed that the removal of one repeat alone remarkably reduced leukemogenicity by the MCF13 virus. A newly identified protein-binding site (MLPal) located within DEN affects transcription only in T cells, and its deletion attenuates the ability of an MCF13 virus with a single enhancer repeat to induce thymic lymphoma. This observation suggests that the MLPal protein-binding site contributes to the effect of the DEN region on T-cell-specific transcription and viral leukemogenicity. This study identifies the importance of nonenhancer sequences in the long terminal repeat for the oncogenesis of the MCF13 retrovirus.
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PMID:Contributions to transcriptional activity and to viral leukemogenicity made by sequences within and downstream of the MCF13 murine leukemia virus enhancer. 133 10

Retroviruses have long been associated with cancer in many species. Human T cell leukaemia virus type I causes adult T cell leukaemia. Human immunodeficiency virus infection is associated with lymphoma and Kaposi sarcoma, but oncogenesis is largely secondary to its effect on the immune system. The incidence of Kaposi sarcoma varies greatly in different social groups with AIDS, being most frequent among male homosexuals; an unknown, sexually transmissible agent may be responsible. Human endogenous retroviral genomes are linked with myeloproliferative disease. Finally, the risk is discussed that cancer could be a side-effect of the use of retroviral vectors in human gene therapy.
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PMID:Retroviruses and human cancer. 133 95

Chromosome abnormalities are found in feline leukemia virus (FeLV)-infected tumor cells as well as in tumor cells free of the virus. Three cell lines derived from tumors in the domestic cat (Felis catus), two of thymic origin and one of multicentric lymphoma origin, were analyzed cytogenetically to determine whether the FeLV virus was associated with chromosomal abnormalities in these tumor cell lines. One thymic tumor and the multicentric lymphoma were FeLV infected. The other thymic tumor cell line was FeLV-free. The normal diploid number in the domestic cat is 38. All three cell lines had numerical chromosome abnormalities with modal numbers of 37, 38 (pseudodiploid), and 39, respectively and had consistent structural chromosome abnormalities. Three markers in the virus-free cell line (S markers) were shared with one or the other of the virus-positive cell lines. The two FeLV-positive cell lines did not have S markers in common. The finding of chromosome abnormalities in both the virus-infected and the virus-free cell lines suggests that these abnormalities may be important in oncogenesis. The FeLV virus could not be considered the only causative agent of the abnormalities observed.
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PMID:Chromosome abnormalities and oncogenesis in cat leukemias. 133 8

A 64 year-old Japanese man who developed acute monoblastic leukemia during the course of adult T-cell leukemia/lymphoma (ATL) was studied. Leukemic cells in the peripheral blood and bone marrow were monoblasts positive for alpha-naphthol butyrate esterase (alpha-NBE) staining, CD11c and CD36 antigens, whereas tumor cells in the pleural effusion were ATL cells positive for CD2, CD4, CD25, CD29 and CD45RA antigens. These two malignant cells had different chromosomal abnormalities. Monoclonal integration of human T-cell leukemia virus type I (HTLV-I) proviral DNA and T-cell receptor C beta gene (TCR C beta) rearrangement were detected in the ATL cells, but not in the leukemic monoblasts. By polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (CD11c+ 98%, CD2+ 4%, CD20+ 0%) not containing ATL cells, the presence of the gag region of HTLV-I was confirmed. These facts indicate that a double positive T cell (CD29+, CD45RA+) was possibly the target cell for HTLV-I infection and that HTLV-I was not directly related to the oncogenesis of the monocyte lineage in the present case, even if it did infect the monocytes. However, there is still an outside possibility that HTLV-I induced acute monoblastic leukemia indirectly.
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PMID:Coexistence of acute monoblastic leukemia and adult T-cell leukemia: possible association with HTLV-I infection in both cases? 133 97

Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. An unusually high incidence of spontaneous thymic lymphoma development was observed after transfer of this mutation from the C.B-17 congenic strain background onto the diabetes-susceptible nonobese diabetic (NOD) background. Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not expressed in the standard substrain NOD/Lt thymus. All tumors exhibited insertions of ecotropic proviruses, whereas only a subset also exhibited proviral integrations of mink cell focus-forming retrovirus. Neither class of retrovirus was associated with consistent integration into genes previously associated with activation of oncogenesis. We propose that the unusual features of T-cell ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted block in thymocyte development, leading to activation of the NOD-unique Emv-30 to initiate thymomagenesis.
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PMID:The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. 137 93

There is abundant evidence that leukemia arise through somatically acquired genetic changes. Familial or congenital predisposition is rarely involved. These genetic changes are often visible as chromosomal aberrations. Molecular analyses of the DNA sequences rearranged in leukemia has demonstrated the presence of cellular oncogenes which are modified (fused, mutated, truncated) by the specific translocations. This results in a disturbance of the delicate balance between proliferation and differentiation and constitute a major step towards cell transformation. Some of these genetic rearrangements have been analyzed in depth, but the exact defect that causes leukemia is often not yet understood. Meanwhile these studies have increased our knowledge of normal cell proliferation and differentiation and provided us with new tools for diagnosis and for developing more specifically targeted treatment. An example would be the production of antibodies that recognize specifically the new chimeric proteins. Oncogenesis is a complex and multiple step process that proceeds by acquisition of successive genetic insults. The different steps do not necessarily occurs following a predetermined order, although some secondary changes are preferentially induced by a given first mutation. In leukemia, sequential changes in karyotype are well documented but molecular makers for tumor progression have not yet been systematically investigated. This is one of our many challenges for the future.
Leukemia 1992 Nov
PMID:Cytogenetics and oncogenes. 143 20

T-cell translocation gene 1 (Ttg-1), also called rhombotin, is deregulated upon translocation into the alpha/delta T-cell receptor loci in acute lymphoblastic leukemias bearing the t(11;14)(p15;q11). Ttg-1 encodes a nuclear protein, expressed predominantly in neuronal cells, which belongs to a novel family of transcription factors possessing LIM domains. We utilized the lck proximal promoter to overexpress this candidate oncogene in immature thymocytes of transgenic mice. lckPr Ttg-1 mice develop immature, aggressive T-cell leukemia/lymphomas. Tumor incidence is proportional to the level of Ttg-1 expression. Most tumors contain CD4+8+ cells as well as CD4-8+ cells, which have an immature rather than a mature peripheral phenotype. Ttg-1-induced tumorigenesis preferentially affects a minority population of thymocytes representing an immature CD4-8+ intermediate stage between double-negative CD4-8- cells and double-positive CD4+8+ cells. This model indicates that the aberrant expression of putative transcription factors plays a primary role in the genesis of T-cell acute lymphoblastic leukemias.
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PMID:Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. 150 13


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