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

We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) alpha- and delta-chain loci. In apparent concert with the translocation, a deletion has occurred between delta-chain diversity (D)-region genes D delta 1 and D delta 2. D delta 2 was observed on derivative chromosome 1 [der(1)] and D delta 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D delta 1-D delta 2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
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PMID:Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript. 246 96

We have compared proviral integrations near (putative) proto-oncogenes in Moloney murine leukemia virus-induced primary and transplanted T cell lymphomas. We previously found proviruses integrated near c-myc, pim-1, and N-myc in primary tumors (Selten et al., 1984; Van Lohuizen et al., 1989a; Van Lohuizen et al., 1989b). We have now identified an additional common proviral integration site, called pim-2, that carries somatically acquired proviruses in the majority of transplanted tumors. In primary tumors integration near pim-2 is usually undetectable or present in only a minor fraction of the tumor cells. This subpopulation selectively grows out upon transplantation. Insertion near pim-2 is a relatively late event in tumorigenesis and is often preceded by proviral insertions in other common insertion sites, yielding tumor clones which carry proviruses in up to three different common insertion sites within the same cell (c-myc, pim-1 and pim-2). The data suggest that pim-2 plays an important role in tumor progression.
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PMID:Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas. 272

In the field of viral oncogenesis the latency period is the interval between detectable establishment of infection and appearance of a tumor. Between 1969 and 1985, a total of 60 sheep died with lymphosarcoma. They were inoculated with BLV-positive blood from various donor cows, by various routes, at various ages, etc. A statistical analysis was performed trying to find a correlation between the length of the latency period and, on the other hand, one or more factors, such as sex, family lineage, identity of the dam, age at inoculation, route of inoculation, or origin of the inoculum. None of the above mentioned parameters has a significant effect on the length of the latency period. In two series of sheep inoculated with decreasing number of lymphocytes from BLV-positive donor cows, hematological disorders and tumors appeared at first in recipient animals inoculated with the higher doses of infectious blood. Thus, the inoculated dose has an effect upon the length of the latency period; the higher the dose inoculated, the shorter the latency period. This finding suggests an explanation to the natural occurrence of multiple case herds as opposed to no-tumor case herds. A multiple case herd fulfills two conditions: the presence of a good donor and an efficient route of transmission allowing the transfer to the recipient of the optimal amount of infected blood.
Leukemia 1988 Feb
PMID:Experimental transmission of enzootic bovine leukosis to sheep: latency period of the tumoral disease. 283 Apr 39

The long terminal repeat (LTR) of the pre-B cell tropic Abelson murine leukemia virus (A-MuLV) was replaced with the LTR of the erythrotropic Friend MuLV or with the LTR of the erythropic/fibrotropic Harvey murine sarcoma virus (Ha-MuSV) to generate the viruses F-ABL and H-ABL, respectively. The parental A-MuLV and the recombinant viruses induced pre-B cell lymphomas in susceptible mice with similar frequencies. Recombinant virus-induced tumor DNAs were analysed by nucleic acid hybridization and were shown to contain the appropriate recombinant provirus. F-ABL was 100-1000 fold less efficient than A-MuLV or H-ABL in the in vitro transformation of primary bone marrow cells, as detected by lymphoid colony formation in agarose. To compare the level of transcription initiated from the different viral LTRs, we investigated the ability of the U3 region of these retroviral LTRs to promote transcription in a battery of cell lines using the chloramphenicol acetyl-transferase (CAT) assay, and with some exceptions we found the following hierarchy of activities: Ha-MusSV greater than or equal to M-MuLV greater than A-MuLV greater than F-MuLV, regardless of the cell line transfected. These results indicate that the LTR is not a determinant of the pre-B cell disease specificity of A-MuLV, and suggest that this specificity resides in the v-abl oncogene. Also, our results suggest that a threshold amount of the v-abl protein product is necessary for in vitro transformation, and this level of expression may be different from the level selected during in vivo tumorigenesis.
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PMID:Substitution of the LTR of Abelson murine leukemia virus does not alter the cell type of virally induced tumors. 283 88

Oncogenes have been intimately associated with the genesis of human neoplasms. A particularly useful system to study the mechanism of tumorigenesis is a small group of avian retroviruses that carry two oncogenes. These viruses causes acute leukemias and can transform hematopoietic cells in vitro. The mechanisms by which viral oncogenes affect the growth control and differentiation of their target cells is now understood in fair detail for two of these virus strains. In the avian erythroblastosis virus AEV, the v-erbB oncogene deregulates the growth control of erythroid precursors, while verbA blocks their terminal differentiation into erythrocytes. Based on the findings that v-erbB oncogene corresponds to a mutated growth factor receptor gene and that v-erbA corresponds to a mutated hormone receptor gene, models have been developed that explain the function of these two oncogenes on a molecular basis. The myelomonocytic leukemia virus MH2 acts by a completely different mechanism. In this case, the v-myc oncogene stimulates the proliferation of macrophage-like cells, while the v-mil gene stimulates them to produce their own growth factor, thus leading to autocrine growth. It will be interesting to determine whether the type of mechanisms of oncogene cooperativity elucidated for acute leukemia viruses are also operative during leukemogenesis in humans.
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PMID:[Oncogenes and the origin of leukemia. Acute avian leukemia viruses]. 284 86

We isolated a novel infectious murine leukemia virus (HoMuLV) from the wild mouse Mus hortulanus. HoMuLV has an ecotropic virus host range, but the viral DNA fails to hybridize to viral envelope segments specific for the known inbred and wild mouse ecotropic as well as nonecotropic MuLVs. Despite this difference in its env gene, HoMuLV appears to use the same ecotropic cell-surface receptor since it infects only hamster and mouse somatic cell hybrids which contain the Rec-1 ecotropic virus receptor on chromosome 5. Furthermore, HoMuLV does not infect mice carrying the Fv-4r allele which is thought to prevent ecotropic virus infection through an interference mechanism. HoMuLV is NB-tropic and, unlike other infectious MuLVs, does not grow in cells derived from the wild mouse species. M. dunni. Five to ten months after neonatal inoculation with HoMuLV, 72% of female NIH Swiss mice (8/11) contracted lymphoma or erythroid leukemia, but 33% of the inoculated males (5/15) developed erythroid or myelogenous leukemia within 8-16 months. These data suggest that NIH Swiss males and females differ in their susceptibility to HoMuLV-induced disease. Furthermore, NIH Swiss mice were found to be more susceptible to HoMuLV-induced disease than NFS/N mice. Tumors contained infectious MCF virus, which is consistent with the hypothesis that MCF virus may mediate tumorigenesis by HoMuLV.
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PMID:HoMuLV: a novel pathogenic ecotropic virus isolated from the European mouse, Mus hortulanus. 284 96

To understand the mechanisms of oncogenesis by human T-cell leukemia virus type I, we have investigated the ability of the tax1, protein to modulate transcription of protooncogenes. By using a transient cotransfection assay, we report that the protooncogene fos promoter is transactivated by tax1 in a variety of cell types. Two regions containing upstream sequences between positions -362/-324 and -323/-276 of the c-fos promoter responded to this activation and also conferred tax1 responsiveness to the heterologous herpesvirus thymidine kinase promoter. These two sequences include elements mediating the induction by v-sis-conditioned medium and serum, phorbol ester, or epidermal growth factor, respectively. Furthermore, expression of the endogenous c-fos gene was activated by tax1 in human T-cell leukemia virus type I-infected cell lines. In contrast, no trans-activation of the c-myc or c-Ha-ras promoter was observed.
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PMID:c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. 284 64

The discovery of the first example of retroviral transduction of an immunological effector molecule has led us to reconsider the possible importance of cell surface receptors of the immune system in leukaemia development. Antigen receptors on lymphoid cells not only bind external ligands but are crucial in the control of cellular proliferation. The concept of autocrine stimulation in oncogenesis is already well established and we see no reason to exclude the possibility of analogous mechanism operating through antigen receptors. At present, we are investigating the oncogenic function of the retrovirus (FeLV-T17) carrying a T-cell receptor gene (v-tcr). In addressing the general concept of oncogenesis by ligand/receptor interactions in the immune system we face the problem of the diversity and, for T-cell antigen receptors, the complex nature of receptor-ligand interaction. Nevertheless, the implications of the model encourage us to continue to search for new experimental tools and approaches to the question.
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PMID:Receptor-mediated leukaemogenesis: hypothesis revisited. 285 66

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.
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PMID:Concurrent adult T-cell leukemia and acute myeloblastic leukemia. 289 97

Spontaneous tumor development and primary oncogenesis were compared in a large number of NK4-deficient, homozygous C57Bl/6-bg/bg mice and their NK normal, heterozygous +/bg littermate controls. In a group of 167 retired breeders followed for spontaneous tumors, the probability of survival for mice eventually dying with a tumor was greater for the NK-competent, +/bg than for the NK-deficient, homozygous C57BL/6-bg/bg mice (p = 0.0019), although the higher overall incidence of tumors in the bg/bg group (48%) was not significantly different from that in the +/bg group (37%). In the bg/bg group the incidence of tumor death appeared to increase relatively sharply in the 25- to 29-month age bracket compared to the fairly regular increase in incidence observed in the +/bg group. All the spontaneous tumors except 2 (discovered in +/bg mice) were classified histologically as widely disseminated malignant lymphomas. The other two were one squamous-cell carcinoma and one sarcoma. A total of 73 bg/bg mice injected s.c. with benzo[alpha]pyrene (BP) had a higher overall incidence of tumors (81%) (rhabdomyosarcomas) than 138 +/bg mice (64%) and in the largest group (0.3 mg, n = 85) the bg/bg group developed tumors, at a higher incidence (p = 0.01) and with a shorter latency (p = 0.025) than the +/bg group. On the other hand, mice injected with dimethylbenzanthracene or given 4 weekly doses of 160 rads of gamma irradiation showed no difference in overall tumor incidence. In addition, mice injected with various doses of DMBA-induced murine leukemia virus (DMBA-LV) also showed no significant difference in tumor incidence. Others have reported that some of these treatments (DMBA, split-dose irradiation) cause profound NK suppression, thereby reducing NK differences between the two groups of mice. These results suggest that a partial NK impairment in beige mutant mice early in life may lead to significantly greater rates of death with spontaneous malignant tumors late in life. Some primary oncogenesis treatments (BP) but not others (DMBA, split-dose irradiation, leukemia viruses) cause tumors with a greater incidence and shorter latency in beige mice. The results suggest, but do not prove, that NK cells play a role in surveillance against spontaneously arising, and possibly some types of carcinogen-induced, tumors.
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PMID:Spontaneous and induced primary oncogenesis in natural killer (NK)-cell-deficient beige mutant mice. 298 10


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