In vitro leukemic cell differentiation in metal-depleted media.

Lymphocytes of children with T cell and pre-B cell acute lymphocytic leukemia (ALL) were cultured in media with different concentrations of Fe, Cu and Zn to detect a possible effect of these ions on leukemic cells. Thymidine uptake was elevated in non-mitogen stimulated ALL cells and increased after mitogen stimulation, whereas intracellular ferritin, Fe and Cu, elevated before culture, decreased thereafter; pre-B ALL cells, positive only for cytoplasmic mu chains, became positive for surface immunoglobulins and released a detectable amount of them; low T4/T8 ratio in cells from T cell ALL returned to normal values after culture. These findings were present only in media with minimal concentrations of Fe, Cu and Zn and suggest that regulation of intracellular levels of these metals may induce some differentiation of leukemic cells.