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

In this report, a Radiation leukemia virus-transformed murine T cell lymphoma is described which is dependent on the interleukin-2 (IL-2) growth factor for proliferation under single cell conditions of growth. It was isolated from a C57BL mouse which had been primed with the Radiation leukemia virus-induced thymoma, C6VL/1, and has been shown to be phenotypically and karyotypically distinct from C6VL/1. IL-2 dependency has been stable over many in vitro passages, and this property also serves to distinguish this cell line from C6VL/1. 5C2 constitutively expresses a T cell receptor (TCR) and can respond by increased proliferation to external stimulation with anti-TCR antibody. This antibody acts to stimulate 5C2 growth in the absence of added IL-2. Maximum stimulation was achieved in the presence of a 50-ng/ml concentration of purified antibody. 5C2 has also been shown to produce detectable levels of IL-2 which can be increased by 8- to 16-fold after exposure of cells to anti-TCR antibody. The C6VL/1 T cell lymphoma has served as a control cell line in three experiments since it cannot be stimulated either to increased proliferation or to lymphokine release by this same antibody. However, a 10-ng/ml concentration of anti-TCR antibody was found to inhibit proliferation of both T cell lymphomas when they were cultured under optimal conditions, i.e., in the presence of an IL-2 source for 5C2. The proliferation of both T cell lymphomas appears to be regulated, although in different ways, by the binding of antibody in the vicinity of the TCR complex. While 5C2 is dependent on IL-2 production (and TCR triggering) to proliferate, C6VL/1 replicates independently of any growth factors. Signal transduction through the TCR/T3 complex, together with the subsequent production of growth factors, may be important for driving the proliferation of T cells such as 5C2 at an early stage in oncogenic progression following infection with an RNA tumor virus.
Leukemia 1988 Feb
PMID:Interleukin-2 and antibody to the T cell receptor regulate proliferation of a radiation leukemia virus-transformed T cell lymphoma. 283 Apr 40

Mouse cell lines of different lineages have been established which constitutively secrete large quantities of recombinant mouse interleukins (mIL2, mIL3, mIL4 or mIL5). An existing bovine papilloma virus-based expression vector, pBV-1MTHA, was modified to allow transformed X63Ag8-653 myeloma cells, NIH 3T3 fibroblasts and C127 mammary tumor cells to stably carry multiple copies of the vector, to express the inserted cDNA encoding a single interleukin constitutively, and to secrete the interleukin in high quantities. Cell lines transformed with mIL2 cDNA stably carried 30-100 copies of the plasmid per cell and constitutively secreted biologically active mIL2 in quantities similar to those produced by murine EL4 thymoma cells or rat spleen cells stimulated with mitogens. Deletion of the 3' untranslated region containing AT-rich sequences from the mIL2 cDNA resulted in a 100-fold increase in the constitutive production and secretion of mIL2 by the transformants. Addition of a heavy metal further increased the production 2 to 6-fold. Cells transformed with 3'-deleted mIL3 cDNA constitutively secreted 300-1000 times higher activities of mIL3 than the myelomonocytic leukemia line WEHI3. mIL4 produced by the similar transformants induced [3H]thymidine uptake of a T cell line, a mast cell line and B leukemia cells, and enhanced the production of IgG1 by B cells. IL4 titers were 150 times higher than those produced by the concanavalin A-stimulated T cell line 2.19. mIL5 was secreted by similar transformants at 10-fold higher titers than those produced by concanavalin A-stimulated 2.19 T cells, as judged by the proliferation and maturation of B cell leukemia BCL1. The expression vectors should be useful in establishing eukaryotic cell lines producing proteins from full length cDNA clones at higher rates. The established cell lines secreting IL2, 3, 4 or 5 at high rate should be useful sources for these interleukins in the investigation of their function in the immune system.
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PMID:Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. 283 Oct 66

In 3 patients suffering from follicular center-cell-derived B-cell lymphoma with primary cutaneous manifestation, antiadult T-cell leukemia-associated antigen antibodies were detected by the ELISA. In one of the patients, the husband and the dog had died from thymoma and from malignant lymphoma, respectively.
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PMID:Antihuman T-cell leukemia/lymphoma virus antibodies in three patients with primary cutaneous B-cell lymphoma. 283 89

p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells. Previous RNase protection data demonstrated the existence of at least two lck mRNAs (type I and type II) with different 5' untranslated regions in most T cells. These have been found here to arise from two separate promoters. S1 nuclease analysis and primer extension were used to locate the site of initiation of type I lck mRNA. The nucleotide sequence of the region upstream of this start site contains no classical promoter motifs. A cDNA clone of type II lck mRNA was isolated. The promoter of this mRNA must be more than 10 kilobases upstream of the type I promoter region. In two murine thymoma cell lines, LSTRA and Thy19, lck is expressed at elevated levels as a result of Moloney murine leukemia virus retrovirus promoter insertion. p56lck is encoded in these cells by a hybrid virus-lck mRNA containing the 5' untranslated region of Moloney virus mRNA. The structures and the sites of integration of the proviruses upstream of lck in these cells were examined by molecular cloning and Southern analysis. A truncated and rearranged provirus, flanked by 554 nucleotides (nt) of duplicated cellular sequences, was found 962 nt upstream of the start site for type I lck mRNA in LSTRA cells. What appears to be a Moloney mink cytopathic focus-forming provirus was found between 584 to 794 nt upstream of the start site for type I lck mRNA in Thy19 cells. Thus in both tumor cell lines, viral DNA is present between the promoters for type I and type II lck mRNAs. Comparison of the sequences of the 5' ends of the lck and c-src genes suggests that divergence of these two genes involved exon shuffling and that a homolog of the neuronal c-src(+) exon is not present in lck.
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PMID:Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters. 284 26

The temporal activities of suppressor T lymphocytes (Ts) and cytotoxic T lymphocytes (CTL) were investigated in a syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma). After the s.c. tumor inoculation, it was suggested that both Ts and CTL were generated with target specificity against 203-glioma cells, because neither Ts nor CTL activity were seen against syngeneic EL 4 (benzpyrene-induced thymoma), allogeneic P815 (methylcholanthrene-induced mastocytoma of DBA/2 mouse origin) or YAC-1 (Moloney leukemia-induced T-cell lymphoma of A/Sn mouse origin), but only against 203-glioma. It was found that the generation of Ts preceded that of CTL and that the turnover was faster; furthermore, Ts were generated in the thymus and spleen, while CTL were distributed in regional lymph nodes and spleen. Surface marker analysis revealed that only Lyt-1-.2.3+ T-cells participated in suppressor responses in contrast to both Lyt-1-.2.3+ and Lyt-1+.2.3+ T-cells participating in cytotoxic responses. The effects of adult thymectomy (ATx) on the changes of the immunized T-cell subsets were also investigated. In mice thymectomized 3 weeks previously, the Ts activity was abrogated, whereas the CTL activity increased markedly and Lyt-1+.2.3+ T-cells were not detected. The results suggest that CTL or their precursors bearing Lyt-1+.2.3+ phenotype and Ts bearing Lyt-1-.2.3+ phenotype are short-lived lymphocytes. Accordingly, it is suggested that in tumor-bearing mice short-lived Ts are generated earliest with target specificity and, due to the reciprocal relationships between Ts and CTL activities, may have a modulating influence on CTL; furthermore, ATx may alter the patterns of generation of the precursor T-cells and Ts.
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PMID:Temporal changes of suppressor T lymphocytes and cytotoxic T lymphocytes in syngeneic murine malignant gliomas. 293 88

The infectious complex of Abelson murine leukemia virus was altered by replacing its usual helper virus, Moloney leukemia virus, with radiation leukemia virus (RadLV). After intrathymic injection of the Abelson-RadLV complex, thymomas arose rapidly, as described previously for injection of the Abelson-Moloney complex. Cell lines were derived from thymomas induced by each Abelson virus complex and were classified according to normal thymus cell phenotypes. Each virus complex induced some cell lines which were like a 0.7% subpopulation of murine thymocytes in that they failed to express the Thy-1 cell-surface antigen. These lines are thus far indistinguishable from some Abelson-derived bone marrow transformants classified as pre-B cells. However, the Abelson-Moloney complex induced some cell lines which expressed low levels of Thy-1 and which shared most markers with immature blast cells of the thymic medulla, whereas the Abelson-RadLV complex induced some lines which were clearly like thymic cortex blast cells. Thus, Abelson virus can induce thymoma cell lines of at least two, and possibly three, distinct phenotypes corresponding to normal thymocyte blast subsets, the determination of which can be influenced by helper virus sequences.
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PMID:Thymocyte subsets transformed by Abelson murine leukemia virus. 298 92

Envelope gp70s were isolated from the thymotropic recombinant viruses related to Moloney murine leukemia virus (RM-M-MuLVs) which were generated by the inoculation of two strains of ecotropic M-MuLV (strain 1869 and temperature-sensitive mutant-1) into BALB/c or CFW/D mice. Chymotrypsin oligopeptide maps of parental ecotropic MuLV, RM-M-MuLV, and inducible xenotropic MuLV showed each of the above virus types had a distinctly characteristic peptide map. The majority of RM-M-MuLV gp70 molecules examined showed a high degree of peptide homology. Data from restriction endonuclease mapping demonstrated that the newly acquired sequences in each of the RM-M-MuLVs were very related and encompassed both the polymerase and the envelope genes. The source of the sequences acquired by the RM-M-MuLV was from endogenous nonecotropic and nonxenotropic proviruses. This suggested that the family of endogenous proviruses which combined with the parental ecotropic virus was either specifically selected or was much more available than other endogenous proviruses. Although slight variations of envelope-specific sequences and peptides existed among various RM-M-MuLV isolates; within a single thymoma, individual clones of tumor cells yielded RM-M-MuLV gp70s which were identical to each other. These findings are discussed within the context of the leukemogenic potential of RM-MuLVs.
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PMID:Thymotropic envelope gene recombinants of Moloney leukemia virus have highly conserved envelope structures. 299 79

Our laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to FXI-induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. In addition not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. Thus, it is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Our studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help us clone and characterize this locus. Currently chromosomal "walking" and "hopping" techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and subtraction hybridization analysis is being used in the search for Ril-1.
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PMID:A molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice. 301 17

The Gross passage A murine leukemia virus (MuLV) induced T-cell leukemia of clonal (or oligoclonal) origin in inoculated mice. To study the role of the integrated proviruses in these tumor cells, we cloned several newly integrated proviruses (with their flanking cellular sequences) from a single tumor in procaryotic vectors. With each of the five clones obtained, a probe was prepared from the cellular sequences flanking the provirus. With one such probe (SS8), we screened several Gross passage A MuLV-induced SIM.S mouse tumor DNAs and found that, in 11 of 40 tumors, a provirus was integrated into a common region designated Gin-1. A 26-kilobase-pair sequence of Gin-1 was cloned from two lambda libraries, and a restriction map was derived. All proviruses were integrated as a cluster in the same orientation within a 5-kilobase-pair region of Gin-1, and most of them had a recombinant structure of the mink cell focus-forming virus type. The frequency of Gin-1 occupancy by provirus was much lower in thymoma induced by other strains of MuLV in other mouse strains. Using somatic-cell hybrid DNAs, we mapped Gin-1 on mouse chromosome 19. Gin-1 was not homologous to 16 known oncogenes and was distinct from the other common regions for provirus integration previously described. Therefore, Gin-1 appears to represent a new common provirus integration region. The integration of a provirus within Gin-1 might be an important event leading to T-cell transformation, and the Gin-1 region might harbor sequences which are involved in tumor development.
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PMID:Identification of a new common provirus integration site in gross passage A murine leukemia virus-induced mouse thymoma DNA. 303 79

Tyrosine protein kinases are important both in the normal regulation of cellular proliferation and in the oncogenic transformation of cells by several tumour viruses. The LSTRA Moloney murine leukaemia virus (M-MuLV)-induced thymoma cell line contains approximately 20-fold more phosphotyrosine in protein than do typical haematopoietic cell lines; this seems to result from the expression of an abnormally high level of a cellular tyrosine protein kinase termed p56tck (refs 3, 4). This kinase is normally expressed at low levels in most, but not all, murine T cells. The elevated levels of p56tck could contribute to the malignant properties of LSTRA cells. Therefore, we have isolated cloned complementary DNAs encoding the whole of p56tck. Sequence analysis shows it to be a novel cellular tyrosine protein kinase which is distinct from all others described to date. p56tck is encoded in LSTRA cells by a hybrid messenger RNA; approximately 200 nucleotides at the 5' end of the mRNA are identical to the 5' end of the genome of M-MuLV. The three- to ninefold transcriptional activation of the gene therefore results from retroviral promoter insertion.
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PMID:Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion. 308 13


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