Integration of Friend murine leukemia virus into both alleles of the p53 oncogene in an erythroleukemic cell line

Hicks, Geoffrey; Mowat, Michael

doi:10.1128/jvi.62.12.4752-4755.1988

Cited by 60 publications

(14 citation statements)

References 33 publications

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“…Another tumor suppresser gene, p53, has also been shown to be inactivated by virus integration in Friend murine leukemia virus-induced erythroleukemias (8,24). As with Nf1, inactivation of the second p53 allele can occur by a nonviral mechanism or by integration of a second provirus.…”

Section: Discussionmentioning

confidence: 99%

Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels

Largaespada

Shaughnessy

Jenkins

et al. 1995

J Virol

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Approximately 15% of BXH-2 myeloid leukemias harbor proviral integrations at the Evi-2 common viral integration site. Evi-2 is located within a large intron of the Nf1 tumor suppressor gene, raising the possibility that proviral integration at Evi-2 predisposes mice to myeloid tumor development by disrupting Nf1 expression. This hypothesis is supported by data suggesting that mutations in the human NF1 gene are causally associated with the development of juvenile chronic myelogenous leukemia (K. M.

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Section: Discussionmentioning

confidence: 99%

Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels

Largaespada

Shaughnessy

Jenkins

et al. 1995

J Virol

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“…To our knowledge, occupation of both alleles of a single gene has never been observed when transcriptional activation is the relevant mechanism. In contrast, insertion at both alleles could occur when the selective advantage is loss of function, as for Friend MuLV insertions at both alleles of the p53 gene (13,32). However, such considerations would not apply to pim-1, which is an activation target (50), and the lack of any instance in our tumor series in which insertions have occurred at both of thefit-1 andpim-1 alleles also argues against such an interpretation.…”

Section: Discussionmentioning

confidence: 86%

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement

Tsatsanis

Fulton

Nishigaki

et al. 1994

J Virol

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The genetic basis of feline leukemia virus (FeLV)-induced lymphoma was investigated in a series of 63 lymphoid tumors and tumor cell lines of presumptive T-cell origin. These were examined for virus-induced rearrangements of the c-myc,flvi-2 (bmi-1),fit-1, and pim-1 loci, for T-cell receptor (TCR) gene rearrangements, and for the presence of env recombinant FeLV (FeLV-B). The myc locus was most frequently affected in naturally occurring lymphomas (32%; n = 38) either by transduction (21%) or by proviral insertion (11%). Proviral insertions were also common atflvi-2 (24%). The two other loci were occupied in a smaller number of the naturally occurring tumors (fit-i, 8%; pim-i, 5%). Examination of the entire set of tumors showed that significant numbers were affected at two (19%Yo) or three (5%) of the loci. Occupation of the fit-i locus was observed most frequently in tumors induced by FeLV-myc strains, whileflvi-2 insertions occurred with similar frequency in the presence or absence of obvious c-myc activation. These results suggest a hierarchy of mutational events in the genesis of feline T-cell lymphomas by FeLV and implicate insertion atfit-i as a late progression step. The strongest links observed were with T-cell development, as monitored by rearrangement status of the TCR n-chain gene, which was positively associated with activation of myc (P < 0.001), and with proviral insertion at flvi-2 (P = 0.02). This analysis also revealed a genetically distinct subset of thymic lymphomas with unrearranged TCR ,8-chain genes in which the known target loci were involved very infrequently. The presence of env recombinant FeLV (FeLV-B) showed a negative correlation with proviral insertion at fit-i, possibly due to the rapid onset of these tumors. These results shed further light on the multistep process of FeLV leukemogenesis and the relationships between lymphoid cell maturation and susceptibility to FeLV transformation.

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“…The genomes of mouse erythroleukaemia cell lines are often associated with the disruption of the ets genes, spi‐1 (PU.1) ( Moreau‐Gachelin et al , 1988 ; Klemsz et al , 1990 ) and fli‐1 ( Ben‐David et al , 1990 , 1991; Sels et al , 1992 ) as well as commonly showing mutations of the tumour suppressor gene, p53 ( Mowat et al , 1985 ; Rovinski et al , 1987 ; Hicks & Mowat, 1988; Ben‐David & Bernstein, 1991; Lu et al , 1994 ) or the fli‐2 locus ( Lu et al , 1994 ). No rearrangements were noted in either the fli‐1 or fli‐2 loci in Bb1 and Bb1‐3, but gross rearrangements were obvious at the p53 (Fig 2A) and spi‐1 (Fig 2B) loci.…”

Section: Resultsmentioning

confidence: 99%

Bb1‐3, a transgenic hybrid cell line with erythroid and megakaryocytic differentiation potential that expresses high levels of human γ‐globin and human β‐globin

1998

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Summary.We have characterized a murine hybrid cell line, Bb1-3, generated by the fusion of mouse primary erythroblasts with MEL cells. It proliferated in serum-free medium and displayed a low level of spontaneous erythroid and megakaryocyte differentiation. Terminal erythroid differentiation could be induced with HMBA and DMSO and was enhanced by serum. Treatment with phorbol esters resulted in a high proportion of megakaryocytes and the expression of megakaryocytic specific lineage markers. Bb1-3 cells contain a human b-globin transgene that was expressed at levels of 20-50% of the endogenous mouse globin genes. Initially, expression was largely limited to the b-globin gene but after adaptation to serum free growth, equal expression of both the human g-and human b-globin genes was observed. This cell line provides further evidence that the differentiation potential of mouse erythroleukaemia cells is not restricted to the erythroid lineage and should be useful to study the mechanisms underlying both developmental globin gene regulation and the terminal differentiation of bipotential erythroid/megakaryocytic progenitor cells.

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Integration of Friend murine leukemia virus into both alleles of the p53 oncogene in an erythroleukemic cell line

Cited by 60 publications

References 33 publications

Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels

Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement

Bb1‐3, a transgenic hybrid cell line with erythroid and megakaryocytic differentiation potential that expresses high levels of human γ‐globin and human β‐globin

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