Ecotropic and mink cell focus-forming murine leukemia viruses integrate in mouse T, B, and non-T/non-B cell lymphoma DNA

Schoenmakers

et al. 1989

Intl Journal of Cancer

The molecular etiology of retrovirally induced T-cell tumors has been shown in many cases to involve proviral integration near a cellular oncogene, c-myc, N-myc, Pim-1 and pvt-1 being frequent targets for insertional activation. Murine B-cell tumors induced by infection with murine leukemia virus have been studied for rearrangements in these and other loci. In contrast to the T-cell lymphomas, tumors of the B-cell lineage, either early B-cell tumors induced in nude mice or late B-cell tumors in immunocompetent mice, did not show disruption of N-myc or Pim-1 in any of the tumors studied, although those lymphomas had acquired many new proviruses. The loci c-abl, bcl-2, fis-1, c-erbB, c-myb, and neu were likewise not involved. Rearrangement of c-myc was seen in 1 out of 71 and rearrangement of the pvt-1 locus in 4 out of 73 (5%) of the B-cell tumors. Thus it appears that mechanistic differences exist in the development of T-cell tumors and B-cell tumors caused by the same etiological agent.

Section: Discussionmentioning

confidence: 94%

“…lc). Viral integrations (la) were examined with an LTR probe specific for the U3 domain (Quint et al, 1984) which cross-reacts with ecotropic and most MCF viruses used in these studies (Zijlstra et al, 1986). Most tumors show multiple clonal proviral integrations, although this is not a strict rule.…”

Section: Southern Analysis Of Long-latency B-cell Tumorsmentioning

confidence: 99%

Retrovirally induced murine B‐cell tumors rarely show proviral integration in sites common in T‐cell tumors

Matthews

Schoenmakers

et al. 1989

Intl Journal of Cancer

“…A polyclonal goat anti-p30 serum (reactive with p30 and its precursor polyproteins) was used in addition to a panel of mAbs reactive with env proteins: anti-gp70f mAb 35/56, and anti-p15E" mAb 19-F8 react with a highly conserved gp70 and p15E epitope, respectively. These epitopes are expressed by both MCF and ecotropic virions and on the cell surface ofMCF and ecotropic virus-infected Location of MuLV specific hybridization probes (derived from references [41][42][43][44] . The positions of some restriction sites are indicated (in kb): K, Kpnl, B, Barn HI; Sm, Sma I, R, Eco RI, Sa, Sau 3a ; P, Pst 1.…”

Section: Resultsmentioning

confidence: 99%

“…Donor (d) and acceptor (a) splice sites are indicated with arrows . Virusspecificity: +, probe hybridizes to (MCF or ecotropic) sequences of the majority of exogenous MuLV; -, probe does not hybridize to (MCF or ecotropic) sequences of the majority of exogenous MuLV (41)(42)(43)(44).…”

Section: Resultsmentioning

confidence: 99%

“…Probes were nick translated with 12 P-dCTP to specific activities of 7-8 x 108 cpm/Feg . The isolation and characterization ofthe MuLVspecific hybridization probes have been described (41)(42)(43). Probes corresponding to the middle and COOH-terminal region ofp15E ofecotropic AKV MuLV (MCp15E probe), the U3LTR of ecotropic AKV MuLV (AKVLTR probe), the NH2-terminal part of the gp70 region of ecotropic AKVMuLV (eco gp70 probe), and the NH2-terminal part of the gp70 region of MCF-MuLV (MCF gp70 probe) were used.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens.

The Journal of Experimental Medicine

Sijts

Leupers

et al. 1989

It is well established that MHC-restricted T cell responses decisively influence the outcome of virus infection (1-3). In the rejection of murine leukemia virus-induced lymphomas, Th and cytotoxic T (Tc) t cells are considered essential effector cells, besides the effects of MuLVspecific antibodies, which can neutralize the virus and inhibit its spread (reviewed in reference 4). Many attempts have been made to characterize the viral antigens that are important in recognition by murine leukemia virus (MuLV)-specific T cells. The presence of viral proteins on the cell surface of MuLV induced tumor cell lines has been documented in a number of serological studies. These cell surface viral proteins, which in processed form are potential target molecules for recognition by Th and Tc cells (5), include the viral env gene-encoded products gPr85env, gp70, and p15(E) and the gag gene-encoded gP95g°g, gP85g°g, p10, pp12, p30, and p15 (reviewed in reference 6). In addition to this, recent data indicate that viral proteins that are not detectable at the surface of cells by serology can also serve as targets for T cells (7). DNA-mediated gene transfer experiments, in which single MuW viral antigens together with particular MHC class I antigens were expressed in heterologous cell lines, and the availability of Tc clones have provided a more subtle analysis of MHC and viral antigen recognition (8, 9). A highly complex picture emerged from these studies, which collectively indicate that both MHC and non-MHC genes determine which viral antigens are recognized in the context of MHC.Recently, substantial progress has been made in the understanding of MHCrestricted recognition ofantigens by T cells. It now appears that T cells usually recognize relatively short antigenic peptides, derived by processing of the native antigen (10, 11). This holds for MHC class II-restricted antigen recognition at the surface of APC by Th cells, but also for MHC class I-restricted antigen recognition by Tc cells, which results in lysis of the antigenic peptide-bearing cells (7,12). The MHCpeptide interaction required for T cell recognition is rather MHC allele specific, which implies that the nature of viral antigens preferentially recognized differs from individual to individual (7,(13)(14)(15)(16)(17) .

Distinct chromosomal abnormalities in murine leukemia virus‐induced T‐ and B‐cell lymphomas

Matthews

Gillis

et al. 1989

Intl Journal of Cancer

We performed a cytogenetic study on 16 murine mature B-cell lymphomas and 10 T-cell lymphomas, using G-banding techniques. All tumors, with the exception of 3 spontaneous B-cell tumors, were induced by various slowly transforming murine leukemia viruses (MuLV). Metaphases were obtained from primary (10 B-cell tumors) and first or second transplant generation lymphomas (6 B-cell and 10 T-cell tumors), all of which were well characterized with respect to phenotypic, histologic and genotypic features. In the T-cell tumors we found relatively simple karyotypic abnormalities, including various numerical aberrations, such as trisomy 15, in line with many earlier reports. However, the majority of B-cell tumors showed a great variety of both structural and numerical chromosomal anomalies. Three B-cell lymphomas had an apparently normal karyotype. No single cytogenetic abnormality occurred commonly in the B-cell lymphomas, but some structural abnormalities were found in more than one stemline, in particular, ins (II) (A1; A2) in 3 tumors, and deletions involving the D-region of chromosome 14 in 3 other lymphomas. These cytogenetic results clearly indicate that the pathogenic mechanisms involved in MuLV-induced (long latency) B-cell lymphomagenesis and (short latency) T-cell lymphomagenesis differ considerably.