CLONAL DOMINANCE OF RADLV-INDUCED LYMPHOMAS

RadLV-induced leukemogenesis begins with the emergence of a pleioclona l population of preleukemic (PL) cells, which subsequently gives rise to a monoclonal lymphoma. We have recently found that the pleioclonal --> monoclonal transition may occur early during the PL latency and lo ng before the eruption of a full blown lymphoma. We sought to find out what causes one PL clone to become dominant. Our working hypothesis w as that a dominant clone(s) at the PL stage has the ability to inhibit the development of other, recessive clones. Since some premalignant c haracteristics of a progenitor clone are probably maintained in the de scending lymphoma, we studied whether tumors that developed after inje ction of a high dose (HD) of PL cells were dominant over tumors that d eveloped after injection of a limiting dose (LD) of PL cells. To ident ify dominant clones, HD and LD lymphomas were mixed in a co-culture an d the outgrowth of one clone over the other was determined by T beta-T CR rearrangement analysis. A checker-board combination of seven lympho mas revealed a dominance hierarchy scale. Lymphomas induced directly b y the virus (without transfer) were dominant over both HD and LD lymph omas. High dose lymphomas were dominant over LD lymphomas and LD lymph omas were always recessive. The speed at which a dominant lymphoma out grew the co-culture suggested that dominance is acquired through the a bility of the prevailing cells to actively suppress the growth of rece ssive cells.