Long-term proliferation of human leukemia cells induced by mouse stroma

Acute lymphocytic leukemias (ALL) of infants and children were found to preferentially survive in coculture with a cloned cell line of endothelial adipose cells (14F1.1) from mouse bone marrow. One of these ALLs expressed a phenotype compatible with an early stage of differentiation (HLA-DR+, CD19+, and CD34+) and exhibited extensive growth in the presence of the mouse stromal cells during a period greater than 25 weeks following seeding. These ALL cells were strictly dependent upon the mouse stromal clone 14F1.1 and failed to proliferate in the absence of the endothelial adipocytes or with a variety of "feeder cells." Throughout the culture period the cells died if removed from the stroma. No similarly proliferative cell population with strict dependence upon stromal cells was found among a variety of other leukemias including hairy cell, acute myeloid, and chronic lymphocytic leukemia. The 14F1.1 clone has been previously found to promote the renewal of mouse and human stem cells. It is therefore possible that leukemias with a stem cell-like phenotype depend upon stromal cell factors similar to those affecting the growth of normal stem cells. These factors appear to operate across genetic barriers.