PROGENITOR TUMORS FROM E-MU-BCL-2-MYC TRANSGENIC MICE HAVE LYMPHOMYELOID DIFFERENTIATION POTENTIAL AND REVEAL DEVELOPMENTAL DIFFERENCES IN CELL-SURVIVAL

Mice expressing both a bcl-2 and a myc transgene within the B lymphoid cell compartment invariably develop novel immature haemopoietic tumou rs. The likely cell of origin of these tumours was identified by a com mon pattern of cell surface marker expression on a subset of cells com prising similar to 1% of normal mouse bone marrow. The bcl-2-myc tumou r cells could be induced to differentiate into either B lymphocytes or macrophages in culture with certain cytokines and feeder cells. Analy sis of their progression into the B lymphoid lineage revealed that Igk locus transcription can precede Igh as well as Igk rearrangement. Sur prisingly, the undifferentiated tumour cells died rapidly in culture, even in the presence of multiple cytokines, but they proliferated on m onolayers of stromal cells derived from haemopoietic tissues. Thus, ev en with Bcl-2 levels that protect more differentiated cells, these imm ature bi-potential progenitor cells require a stromal-induced signal f or survival. These results provide insight into the process of lineage commitment and suggest new levels of control of cell survival during early steps in haemopoietic development.