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

Human papillomavirus type 16 (HPV type 16) has been implicated as an etiological agent in human cervical cancer. This virus contains sequences which, under the proper transcriptional control, can increase the tumorigenicity of established mouse cells and cooperate with EJ-ras in transforming primary baby rat kidney (BRK) cells. These data argue that this virus contains oncogenic sequences. Because this is a human virus, it was important to study the effect on primary human cells of HPV type-16 DNA in both the presence and absence of EJ-ras. We now present data which demonstrate that HPV type-16 DNA, under the transcriptional control of Moloney murine leukemia viral long terminal repeats (MoMuLV-LTR), can extend the life span of primary human fibroblast cells in culture. Co-transfection of the HPV type-16 DNA containing plasmid together with an activated EJ-ras oncogene gives rise to transformed cells which grow faster, are morphologically different from and more aneuploid than cells established with only HPV type-16 DNA. Molecular analysis of these established and partially transformed human cells reveals that they contain and express the transfected DNA. These data argue that primary human cells can be transformed with HPV type-16 and EJ-ras sequences, whereas cells harboring only HPV type 16 DNA are largely normal but have an extended life span.
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PMID:Transformation of primary human fibroblast cells with human papillomavirus type 16 DNA and EJ-ras. 284 Dec 48

The Harvey murine sarcoma virus genome contains two rat-derived sets of genetic information recombined with the Moloney mouse leukemia virus. The rat sequences represent a ras oncogene and a rat VL30 element. The VL30 sequences have several discrete regions of similarity with retroviral sequences which were detected by searching a protein database for similarities with predicted polypeptide sequences from the VL30 regions. On the 5' side, the most similar sequences were those of feline sarcoma viruses; on the 3' side, murine leukemia viruses were the most similar. Some of the regions of similarity could also be detected directly by searching a nucleic acid sequence database with the viral DNA sequences. The most extensive region of similarity was that which corresponded to the endonuclease in the pol gene of a murine leukemia virus. The majority of the rat-derived sequences present in the Harvey sarcoma virus genome can now be attributed exclusively to ras or retrovirus- or retrotransposon-related sequences.
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PMID:Harvey sarcoma virus genome contains no extensive sequences unrelated to those of other retroviruses except ras. 284 4

The oncogenes coding for the Harvey murine sarcoma virus p21ras protein as well as those coding for myc, myb, and mht products were fused to the amino-terminal portion of the bacteriophage lambda cII gene on the expression vector pJL6. In addition two regions of the gene for the human T-cell leukemia virus subgroup I (HTLV-I) envelope were expressed in our bacterial system. Each of 11 human sera tested that had been shown to contain antibodies to HTLV-I or -II by an enzyme-linked immunosorbent assay recognized the bacterially synthesized envelope proteins. No reaction was detected when 17 control sera were tested. This system will be useful for large-scale seroepidemiological surveys for HTLV-I and related human retroviruses. The other oncogene products expressed in our bacterial vector system also demonstrated specific immunoreactivities. In addition to this feature the bacterial ras protein was seen to bind guanosine diphosphate and was capable of autophosphorylation. Taken together these data suggest that the proteins produced with high efficiency by the bacterial expression system can be immunologically recognized as antigens and can in part perform some of their associated biochemical functions.
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PMID:Production of oncogene-specific proteins and human T-cell leukemia (lymphotropic) retrovirus (HTLV-I) envelope protein in bacteria and its potential for use in human cancers and seroepidemiological surveys. 286 93

We have determined the prevalence of amplification and rearrangements for c-myc, c-myb, c-mos, bcr, c-abl, c-Ha-ras-1, c-N-ras, and c-K-ras-2 in a total of 51 cases of human leukaemia (19 patients with AML, 13 cases with CML, 14 cases with ALL, and 5 cases with CLL). Amplifications at a level of more than 2 two copies per haploid genome are apparently very rare and were found only once for c-myb in a c-ALL patient. Oncogene rearrangements were not found except for bcr, which was rearranged in all cases of CML, and 5 cases of ALL studied. Restriction fragment lengths polymorphisms (RFLPs) were also analysed. A previously described rare 5 kb EcoRI allele at the c-mos locus was absent in our patients. Rare alleles at the c-Ha-ras-1 locus were found to be significantly more prevalent in our patients than in a control group. Transfection experiments revealed no dominant transforming oncogenes in the tumour DNA of 3 patients carrying such rare alleles.
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PMID:Oncogene amplifications, rearrangements, and restriction fragment length polymorphisms in human leukaemia. 288 56

Tiazofurin (2-beta-D-ribofuranosyl-4-thiazole-carboxamide; NSC 286193), an antitumor carbon-linked nucleoside that inhibits IMP dehydrogenase (IMP:NAD+ oxidoreductase; EC 1.1.1.205) and depletes guanylate levels, can activate the erythroid differentiation program of K-562 human leukemia cells. Tiazofurin-mediated cell differentiation is a multistep process. The inducer initiates early (less than 6 hr) metabolic changes that precede commitment to differentiation; among these early changes are decreases in IMP dehydrogenase activity and in GTP concentration, as well as alterations in the expression of certain protooncogenes (c-Ki-ras). K-562 cells do express commitment-i.e., cells exhibit differentiation without tiazofurin. Guanosine was effective in preventing the action of tiazofurin, thus providing evidence that the guanine nucleotides are critically involved in tiazofurin-initiated differentiation. Activation of transcription of the erythroid-specific gene that encodes A gamma-globin is a late (48 hr) but striking effect of tiazofurin. Down-regulation of the c-ras gene appears to be part of the complex process associated with tiazofurin-induced erythroid differentiation and relates to the perturbations of GTP metabolism.
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PMID:Induction of erythroid differentiation and modulation of gene expression by tiazofurin in K-562 leukemia cells. 290 Nov

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.
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PMID:Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. 291 75

Injection of newborn mice with mixtures of wild-type moloney murine leukemia (Mo-MuLV) virus and other recombinant retroviruses harboring the myc oncogene alone or in combination with the H-ras oncogene resulted in a 100% incidence of lymphatic leukemias from which permanent cell lines could be established in vitro. These cells are immunoglobulin (Ig)-, Thy-1+BP- and CD8-CD4- indicating that they are early thymocytes. Such transformed pre-T lines lack retroviral myc and ras genes but occasionally possess proviral insertion near to their endogenous myc and pim genes. We show that both Ig heavy chain (Igh) and T cell receptor (TcR) genes are rearranged in most of these lines. In some cases, a primary recombination was followed by a secondary rearrangement at the same locus. We show that VT gamma genes can rearrange outside of their known cluster suggesting that TcR gamma diversification in such pre-T cells may be different to that in more mature T cells. Ig D-JH recombinations may precede TcR gene recombination in these early T cell lines, and some but not all express sterile Cmu transcripts. Some of these lines express surface heterodimers that appear composed of alpha and beta chains that can be immunoprecipitated with a monoclonal anti-T3 antibody but not with the anti-V beta 8 monoclonal antibody F23.1. This established pre-T cell line represents novel biological material for the dissection of T cell development and function analogous to A-MuLV transformed pre-B cells.
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PMID:Rearrangement and expression of T cell receptor and immunoglobulin loci in immortalized CD4-CD8- T cell lines. 296 19

Early-passaged rat chondroblasts (RX cells) and embryonal fibroblasts (RE cells) are hardly transformed by transfection of activated human H-ras (EJras) or by Abelson murine leukemia virus v-abl oncogene. However, these cells were transformed by v-abl or EJras gene when dexamethasone (DX) was added in the culture medium as well as when co-transfected with retrovirus LTR-linked mouse c-myc gene. RX cell lines carrying v-abl (RXabl), RE cell lines carrying v-abl (REabl) and RX cell lines carrying EJras (RXEJ) were established from transformed colonies in the DX-added soft agar. In the absence and in the presence of DX, RXabl cells showed mortal and immortalized, REabl cells showed mortal and transformed, and RXEJ cells showed immortalized and transformed phenotypes, respectively. Especially, immortalization and transformation of REabl1 and REabl3 lines were switched on and off by addition and depletion of DX. v-abl or EJras mRNA levels in tested REabl, RXabl and RXEJ lines cultured without DX was not decreased compared to those cultured with the hormone. The above suggests that, like myc gene, glucocorticoid collaborates with v-abl or activated ras oncogene to transform unestablished rat cells and that the transformation phenotypes were determined not only by the introduced oncogene but by the cellular condition including their tissue origin. Transformation of senescent REabl cells in the absence of DX was tested by transfecting different oncogenes. Among nuclear oncogenes tested, only adenovirus 12 E1A gene could induce transformation of G0-arrested REabl cells in a cooperative fashion with the integrated v-abl gene.
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PMID:Conditional immortalization and/or transformation of rat cells carrying v-abl or EJras oncogene in the presence or absence of glucocorticoid hormone. 297 44

High-molecular weight DNAs of fresh bone marrow cells from 32 patients with fresh leukemia were assayed for the presence of transmissible activated transforming genes by a DNA-mediated gene transfer technique using NIH/3T3 cells. DNAs of bone marrow cells from four of the 32 patients induced transformation of NIH/3T3 cells. Two of the four cases, a chronic myelogenous leukemia and an acute lymphocytic leukemia, contained activated N-ras oncogenes. Molecular cloning and nucleotide sequence analysis revealed that the lesion responsible for the transforming activity was localized to a single nucleotide transition from guanine to thymine in codon 12 of the predicted protein in each of the two cases. These observations indicate that activation of N-ras oncogenes is independent of the specific stage of cell differentiation or the leukemia phenotype. The other two transforming genes associated with an acute myelogenous leukemia and an acute lymphocytic leukemia showed homology neither with members of the ras gene family nor with the human Blym-1 gene. Thus, the NIH/3T3 transfection assay frequently detects activated N-ras oncogenes in human leukemias, while other transforming genes, distinct from the ras gene family, can be detected in some leukemias by the transfection assay.
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PMID:Transforming genes in human leukemia cells. 299 10

Internal irradiation of mice using bone seeking radionuclides results in the activation of endogenous retroviruses and in the subsequent development of bone tumors. Genomic DNA from an osteosarcoma cell line, derived from an 90Sr-induced bone tumor, was cotransfected with the plasmid pSV2-neo into NIH/3T3 cells and G418-resistant transfectants gave rise to colonies in soft agar. Southern blot analysis of these first cycle transformants revealed the presence of extra copies of c-ras. We have analysed the arrangement of ecotropic murine leukemia proviral sequences in seven 90Sr-induced bone tumors and one osteosarcoma cell line of CF1-mice. Integration of ecotropic and/or ecotropic recombinant proviruses seems to be involved in rearrangements of 3' provirus cellular junction fragments occurring in all tumor DNAs analysed, but no indication for site-specific integration was found. We also determined the primary structure of FBR-MuSV, a transforming retrovirus able to induce bone tumors in newborn mice. FBR-MuSV contains sequences from all four exons of the murine c-fos gene, but lacks sequences encoding the first 24 and the last 98 amino acids of the c-fos gene product. The coding region of FBR-MuSV has also undergone two small in frame deletions. Thus, the v-fosFBR-MuSV retains 236 amino acids of the 380 amino acids of the murine c-fos product. In FBR-MuSV-transformed cells two fos-containing mRNAs have been detected: a 3.3-kb full-size genomic RNA and a 2.2-kb subgenomic mRNA as revealed by both fos- and MuLV-hybridization probes.
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PMID:Oncogene involvement in radiation- and virus-induced mouse osteosarcomas. 301 18


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