In a previous paper we described the induction by x-irradiation or
radiation-induced leukemia virus-inoculation of two classes of lymphoid T-cell
neoplasms: The first class, designated T-cell lymphoblastoma (TCLB), consists of
growth-factor-dependent eudiploid cells that home to the spleen and give rise to splenic
tumors on injection into syngeneic mice; the second class, designated
T-cell lymphoma (TCL), consists of
growth-factor-independent
aneuploid or pseudodiploid cells that give rise to local
tumors at the site of
subcutaneous injection. This paper describes the generation of a family of
growth-factor-independent
aneuploid or pseudodiploid TCL cells after the injection into the thymus of
growth-factor-dependent diploid TCLB cells. In contrast to the donor TCLB cells, the resulting TCL cells could be cloned in semisolid medium, produced local
tumors at the site of
subcutaneous injection, and proliferated in a
growth-factor-independent fashion in vitro. The induced
growth-factor-independent TCL cells were chromosomally and phenotypically unstable and continued to evolve both in vivo and in vitro. After propagation in the thymus, the cells often showed stable translocations in addition to the evolving
aneuploidy. We propose that the
chromosome abnormalities induced during the proliferation of
growth-factor-dependent TCLB cells in the thymus constitute a general mechanism by which neoplastic cells progress from
growth-factor dependency to independency.