Expression in irradiated MEFs exposed to murine acute lymphoblastic leukemia cells

Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs. We isolated RNA from irradiated wild-type MEFs after a 9-day culture period. MEFs had either been exposed to DMSO, to nilotinib, a drug that is not expected to affect them, or to ALL cells treated with DMSO or nilotinib. MEFs and ALL cells were physically separated by a Transwell membrane of a pore size that did not allow the ALL cells to migrate towards the MEFs, but allowed the exchange of diffusible molecules.