In vitro colony forming and liquid cultures were used to study humoral factors affecting acute nonlymphocytic leukemia (ANLL) cell growth. Previous studies examined effects of steroid hormones (androgens, estrogen, and hydrocortisone) on acute nonlymphocytic leukemia liquid culture and colony growth and effects of prostaglandin E on chronic myelogenous leukemia granulocyte/macrophage progenitor growth. A survey study showed colony stimulating factor (CSF) response by human ANLL cells in both colony and liquid culture and showed inferential evidence for the existence of active non-CSF compounds in PHA leukocyte-conditioned media. Effects of anti-transferrin receptor (anti-TfR) monoclonal antibodies on acute nonlymphocytic leukemia cells were studied, and inhibitory effects demonstrated. Mechanisms of anti-TfR growth inhibition are currently under study. Concentrated media conditioned by ANLL cell lines were also studied for effects on ANLL cell growth. An active factor was detected, and further investigation showed this factor to be human transferrin (Tf). Tf enhanced CSF release from normal adherent blood and bone marrow cells. Characterization of cells mediating this effect is in progress. Tf also increased ANLL cell growth, but the mechanism is unclear at present. Other current studies include examination of effects of purified erythrocyte potentiating activity (EPA, BPA) and fractionated Mo-T cell media on ANLL colony and liquid culture growth. The goal of these studies is to detect non-CSF agents enhancing leukemia cell growth. To further study anti-TfR inhibition of leukemia cell growth and to define the roles of iron in transferrin in the growth of these cells, HL-60 cells have been adapted to serum-free, Tf-free culture. Preliminary evidence indicates anti-transferrin receptor antibodies do not inhibit these cells and that anti-TfR inhibition occurs by blocking iron uptake. Further efforts to test models of transferrin's effects and effects of CSF on ANLL cells are in progress. These include use of long-term leukemia ANLL cultures with various irradiated feeder cells. The goals of this project remain delineation of humoral effects of ANLL growth and contrast of ANLL responses to normal granulocyte/macrophage progenitors. (N)