Clonal dominance of RadLV-induced lymphomas.
RadLV-induced leukemogenesis begins with the emergence of a pleioclonal 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 long before the eruption of a full blown lymphoma. We sought to find out what causes one PL clone to become dominant. Our working hypothesis was that a dominant clone(s) at the PL stage has the ability to inhibit the development of other, recessive clones. Since some premalignant characteristics of a progenitor clone are probably maintained in the descending lymphoma, we studied whether tumors that developed after injection of a high dose (HD) of PL cells were dominant over tumors that developed after injection of a limiting dose (LD) of PL cells. To identify dominant clones, HD and LD lymphomas were mixed in a co-culture and the outgrowth of one clone over the other was determined by T beta-TCR rearrangement analysis. A checker-board combination of seven lymphomas revealed a dominance hierarchy scale. Lymphomas induced directly by the virus (without transfer) were dominant over both HD and LD lymphomas. High dose lymphomas were dominant over LD lymphomas and LD lymphomas were always recessive. The speed at which a dominant lymphoma outgrew the co-culture suggested that dominance is acquired through the ability of the prevailing cells to actively suppress the growth of recessive cells.
Avni
O
O
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yefenof
E
E
Kotler
M
M
D000818:Animals; D018920:Coculture Techniques; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000473:pathology; D011289:Preleukemia / Q000235:genetics / Q000473:pathology; D016721:Radiation Leukemia Virus; D012192:Retroviridae Infections / Q000235:genetics / Q000473:pathology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology*