One of the toxic effects of anti-cancer and anti-HIV chemotherapy is thrombocytopenia. The colony forming unit-megakaryocyte (CFU-Meg) is a measure of the number of marrow progenitor cells capable of proliferating and differentiating into a megakaryocyte colony. This assay is useful in evaluating the contribution of known (i.e., IL-6, steel factor, IL-3) and experimental (i.e., Meg-CSF) cytokines to megakaryocyte production. Megakaryocytes remain in the marrow and release platelets into the bloodstream to assist in clotting. A defined, sensitive CFU-Meg assay, can be adapted for use in: 1) measuring the toxicity of anti-HIV and anti- cancer drugs on megakaryocyte precursors, 2) determining the CFU-Meg capacity of bone marrow harvested for transplant or 3) identifying the presence of Megakaryocyte colony-stimulating factor (Meg-CSF) for purification purposes. The feasibility study described in this Phase I SBIR proposal will develop a megakaryocyte progenitor (CFU-Meg) assay composed only of well-defined components and optimized by the addition of recombinant cytokines. Both early acting cytokines (i.e., steel factor, IL-11) to increase the proliferation of progenitor cells and late acting cytokines (i.e., IL-6) to increase differentiation of mature megakaryocytes will be added in combination.
