Sugiyama H, Silva S, Wang Y S, Weber G, Babonits M, Rosén A, Wiener F, Klein G
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Int J Cancer. 1990 Nov 15;46(5):845-52. doi: 10.1002/ijc.2910460516.
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.
将携带E mu - myc转基因的小鼠与BALB/c小鼠回交至回交第3代。将后代（其中携带转基因和不携带转基因的小鼠比例大致相等）随机分为2组。34只小鼠（第I组）先用 pristane 处理，然后接种A - MuLV，40只（第II组）仅注射A - MuLV。第I组共发生16例淋巴样肿瘤，第II组发生17例。第I组9例肿瘤和第II组4例肿瘤表现为腹水瘤。腹水中含有淋巴母细胞和10%至45%的浆细胞样细胞。这些肿瘤被指定为浆母细胞淋巴瘤（PLs）。除1例肿瘤外，所有肿瘤均为转基因阳性且无易位。第I组的1例特殊肿瘤携带6;15易位变体但不携带转基因。它显然对应于常规的Abelson + pristane诱导的浆细胞瘤。在11例检测的PLs中，10例有单个逆转录病毒插入位点，而1例肿瘤有3个插入位点。在连续回交过程中随机选择的18只未处理的转基因后代（第III组）中，15只（83%）发生淋巴瘤，无浆细胞样分化迹象。假设第I组和第II组50%的小鼠为转基因小鼠，则3组的发病率相当。肿瘤发生的时间分布也相似。将无淋巴瘤临床症状的携带转基因小鼠的脾细胞在体外感染A - MuLV，并经腹腔注射移植到BALB/c受体小鼠体内。在31例用pristane处理的受体小鼠中有26例发生PLs，但在18例未处理的受体小鼠中仅1例发生。检测的6例PLs中有1例是单克隆的，其余5例是寡克隆的。它们均表达v - abl。这些结果表明，一些组成型表达活性myc转基因的肿瘤前B细胞在感染A - MuLV后转变为浆母细胞。pristane - 肉芽肿的存在促进了它们肿瘤潜能的充分发展。
