Control of in vivo differentiation of myeloid leukemic cells

The differentiation of leukemic cells in vivo can be a useful approach to therapy. In vivo differentiation of myeloid leukemic cells was studied in intraperitoneally implanted diffusion chambers, containing different soluble antigens. The presence of these antigens in the chambers induced differentiation of myeloid leukemic cells and this was inhibited in immune-deficient mice. Transfer of normal spleen cells enriched for T-lymphocytes or antigen-specific helper T lymphocyte cell lines to mice in which differentiation of leukemic cells was inhibited, restored in vivo differentiation of the leukemic cells. Antigen-specific helper T cells produce myeloid regulatory proteins and can accumulate at a site that contains the specific antigen. It is suggested that migration in response to antigen of helper T cells producing regulatory proteins may play an important role in inducing in vivo differentiation of leukemic cells. We have identified a class of myeloid leukemic cells that can be induced to differentiate in vitro by incubation with pure MGI-1GM (GM-CSF) or IL-3, but not with MGI-1G (G-CSF). Experiments with pure recombinant proteins have shown that MGI-1GM and IL-3, but not MGI-1G, can also induce these myeloid leukemic cells to differentiate in vivo. These results and our previous studies on the myeloid cell differentiation-inducing protein MGI-2, demonstrate the potential use of normal hematopoietic regulatory proteins not only in regulation of normal hematopoiesis, but also in the treatment of myeloid leukemia by in vivo induction of terminal cell differentiation.