Deregulated c-myc expression is insufficient for emergence of the tumorigenic phenotype in malignancy-suppressed intratypic T-cell lymphoma hybrids: an in vitro model for multistep lymphomagenesis.

Abstract

The T-cell lymphoma cell line YACUT was fused with the Mls-1a antigen-responsive non-tumorigenic T-cell line G4 to construct growth-arrested hybrids which could be induced to proliferate in the presence of Mls-1a antigen. Prolonged growth of the hybrids by repeated antigenic stimulation resulted in the emergence of cells with transformed phenotype, which was accompanied by a reversion of c-myc expression to the levels of the YACUT lymphoma parent and an increase in the number of YACUT-derived chromosome 15 carrying the rearranged pvt-1 gene. Despite these two changes, early passage transformed hybrids as well as proliferation-suppressed hybrids were non-tumorigenic in vivo. The fact that only late passage transformed hybrids produced tumors in vivo indicated that additional genetic and/or epigenetic alterations are required for the emergence of hybrid lines with tumorigenic phenotype. Thus, this experimental system offers tangible possibilities for delineation of the three distinct phenotypes which could be exploited for the investigation of the multistep process of lymphomagenesis.