Abelson murine leukemia virus transforms preneoplastic Emu-myc transgene-carrying cells of the B-lymphocyte lineage into plasmablastic tumors.
E mu-myc transgenic mice were back-crossed to BALB/c mice up to back-cross generation 3. The offspring that included transgene-carrying and -negative mice in approximately equal proportions were randomly divided into 2 groups. Thirty-four mice (group I) were treated with pristane, followed by A-MuLV, and 40 (group II) were injected with A-MuLV alone. Altogether, 16 lymphoid tumors developed in group I and 17 in group II. Nine of the tumors in group I and 4 in group II appeared as ascitic tumors. The ascites contained lymphoblasts and 10 to 45% plasmacytoid cells. These tumors were designated as plasmablastic lymphomas (PLs). All tumors except one were transgene-positive and did not carry translocations. An exceptional tumor in group I carried a variant 6;15 translocation but not the transgene. It obviously corresponds to the regular Abelson + pristane-induced plasmacytoma. Among 11 tested PLs, 10 had a single retroviral insertion site, while one tumor showed 3. Among 18 untreated transgenic descendants (group III), chosen randomly during serial back-crosses, 15 (83%) developed lymphomas, with no sign of plasmacytoid differentiation. The incidence was comparable in all 3 groups, assuming 50% of the mice in groups I and II to be transgenic. The time distribution of tumor development was also similar. Spleen cells from transgene-carrying mice with no clinical sign of lymphoma were infected in vitro with A-MuLV and transplanted i.p. into BALB/c recipients. PLs developed in 26 of 31 pristane-treated recipients, but in only one of 18 untreated recipients. One of 6 PLs tested was monoclonal, whereas the remaining 5 were oligoclonal. They all expressed v-abl. These results show that some of the preneoplastic B-cells that expressed constitutively active myc transgene turned into plasmablasts after infection with A-MuLV. Full development of their neoplastic potential was facilitated by the presence of pristane-granuloma.
Sugiyama
H
H
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Silva
S
S
Wang
Y S
YS
Weber
G
G
Babonits
M
M
Rosén
A
A
Wiener
F
F
Klein
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D002273:Carcinogens / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000209:etiology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics*; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000209:etiology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D012190:Retroviridae; D013154:Spleen / Q000166:cytology / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology; D014412:Tumor Virus Infections / Q000150:complications
D002273:Carcinogens; D013729:Terpenes; C009042:pristane