Miller M, Kennewell A, Symonds G
Leukemia Research and Viral Pathology Unit, Children's Medical Research Foundation, Camperdown, Sydney, NSW, Australia.
Leukemia. 1992 Jan;6(1):18-28.
v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia.
v-erb-B是禽成红细胞增多症病毒的主要转化基因，禽成红细胞增多症病毒是一种复制缺陷型逆转录病毒，它能在体外转化红细胞和成纤维细胞，并在体内引发红白血病和纤维肉瘤。我们使用了一种重组鼠逆转录病毒，其基于莫洛尼鼠白血病病毒的截短基因组，并包含嵌合的gag-v-erb-B基因，来确定由v-erb-B转化的鼠造血细胞。用这种病毒感染液体培养中的第16.5天鼠胚胎细胞，导致松散至非贴壁造血细胞集落的生长，这些细胞与贴壁单层细胞紧密相关地生长。培养数周后，从这个虽然仍依赖生长因子但已启动转化的群体中出现了转化前B淋巴细胞的克隆群体。这些转化细胞不依赖生长因子，并且在同基因小鼠中具有致瘤性。结果表明，尽管v-erb-B可以启动鼠造血细胞的转化，但建立完全转化的不依赖生长因子、具有致瘤性的表型还需要其他事件。这种v-erb-B诱导的从依赖生长因子到不依赖生长因子的进展为分析白血病起始和维持过程中涉及的事件提供了一个体外模型系统。
