MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes

Viability-promoting genes such as BCL2 play an important role in human canc er but do not directly cause aggressive tumors, BCL2 transgenic mice develo p lymphoma at low frequency, hindering studies of tumorigenesis and its inh ibition in the presence of such gene products. MCL1 is a mem ber of the BCL 2 family that is highly regulated endogenously and that promotes cell viabi lity and immortalization when introduced exogenously, Mice expressing an MC L1 transgene in hematolymphoid tissues have now been monitored for an exten ded period and were found to develop lymphoma with long latency and at high probability (more than 85% over 2 years). In most cases, the disease was w idely disseminated and of clonal B-cell origin, A variety of histologic sub types were seen, prominently follicular lymphoma and diffuse large-cell lym phoma. MCL1 thus sets the stage for the development of lymphoma as does BCL 2, disease occurring with high probability and recapitulating a spectrum of subtypes as seen in human patients. These findings with the transgene unde rscore the importance of the normal, highly regulated pattern of MCL1 expre ssion, in addition to providing a model for studying tumorigenesis and its inhibition in the presence of a viability promoting BCL2 family member. (C) 2001 by The American Society of Hematology.