Abelson murine leukemia virus transforms preneoplastic Eμ‐myc transgene‐carrying cells of the B‐lymphocyte lineage into plasmablastic tumors

Abstract

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.