BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.

Abstract

BALB- and Harvey-murine sarcoma viruses (MSV) comprise a family of retroviruses whose mouse- and rat-derived onc genes are closely related. These viruses induce sarcomas and erythroleukemias in susceptible animals. An in vitro colony assay that detects transformation of lymphoid cells by Abelson-murine leukemia virus was used to demonstrate that BALB- and Harvey-MSV transform a novel hematopoietic cell both in culture and in vivo. Bone marrow colony formation was sarcoma virus dependent, followed single-hit kinetics, and required the presence of mercaptoethanol in the agar medium. BALB- and Harvey-MSV-induced colonies could be established in culture as continuous cell lines that demonstrated unrestricted self-renewal capacity and leukemogenicity in vivo. The cells had a blast cell morphology and lacked detectable markers of mature cells within the myeloid or erythroid series. They also lacked detectable immunoglobulin mu chain or Thy-1 antigen, markers normally associated with committed cells of the B and T lymphoid lineages, respectively. However, the transformants contained very high levels of terminal deoxynucleotidyl transferase (TdT), an enzyme believed to be specific to early stages within the lymphoid differentiation pathway. This phenotype distinguishes these BALB- and Harvey-MSV transformants from any previously reported hematopoietic targets of transforming retroviruses, including the pre-B lymphoid cell transformed by Abelson-MuLV under identical assay conditions. These newly identified lymphoid progenitor cell transformants may provide an important means of studying early stages of lymphoid ontogeny and the possible role of TdT in lymphoid development.

Myeloid cell transformation by ras-containing murine sarcoma viruses.

“…Two types of morphologically distinct colonies were detected in the bone marrow colony-forming assay after infection with BALB or Harvey MSV. As previously reported (34), one colony type that arose after infection with these ras-containing MSVs was compact in morphology and required the presence of 50 ,uM mercaptoethanol in the soft agar medium. Compact colonies consisted of lymphoid progenitor cells, which could be established into continuous lines that exhibited unrestricted self-renewal in vitro and tumorigenicity in vivo.…”

“…These findings, in addition to previous evidence for ras gene-induced growth alterations of lymphoid and erythroid cell types (17,34), provide evidence that ras genes can alter the growth and differentiation of hematopoietic target cells within each of the major hematopoietic differentiation pathways.…”

“…1). Whereas compact colony formation was entirely dependent on the presence of 50 p.M mercaptoethanol (34), the induction of diffuse colonies did not require mercaptoethanol. There was a linear relationship between the number of diffuse colonies formed and the amount of virus inoculated (Fig.…”

“…These viruses induce sarcomas and transform fibroblasts in tissue culture (1,19,25) as well as alter the growth and differentiation of epithelial cells (55) and certain hematopoietic cells (17,34). One well-characterized hematopoietic target of ras oncogenes is a subset of cells within the early lymphoid differentiation pathway which are induced to undergo unrestricted self-renewal and neoplastic conversion in vitro and in vivo in response to these viruses (34). ras-containing viruses can also alter the growth of erythroid cells, inducing erythropoietin-dependent proliferation.…”

Insertion of the v-Ha-ras oncogene induces differentiation of calcitonin-producing human small cell lung cancer

“…In many cell types, ras gene overexpression or mutation is associated with neoplastic transformation or progression (5,(16)(17)(18)(19)(20)(21)(22)(23). However, previous studies in two well-defined neuroendocrine tumor cell lines, rat pheochromocytoma cell line PC 12 (6)(7)(8) (24).…”