Lactoferrin, transferrin and acidic isoferritins: regulatory molecules with potential therapeutic value in leukemia.

In the process of evaluating roles for purified preparations of lactoferrin, transferrin and acidic isoferritins in the regulation of myelopoiesis, it was found that: (1) values reported for lactoferrin in the serum and plasma of normal donors are in most cases an over-estimation, (2) lactoferrin suppresses the production/release of granulocyte-macrophage colony stimulatory factors (GM-CSF) from monocytes in the absence of T-lymphocytes and also suppresses the production/release of acidic isoferritin-inhibitory activity from monocytes, (3) lactoferrin, transferrin and acidic isoferritins act on their specific target cells which express Ia-like antigens, (4) lactoferrin and transferrin act in vivo to suppress rebound myelopoiesis in mice recovering from sublethal dosages of Cytoxan, with preliminary observations suggesting that lactoferrin has a greater apparent effect on the bone marrow and transferrin has a greater apparent effect on the spleen, (5) active lactoferrin derives from Fc receptor positive subpopulations of PMN from patients with CML as well as from normal donors, but the percentage of Fc receptor containing PMN is lower in CML, as is the amount of active lactoferrin found in their PMN, and (6) lactoferrin, transferrin and acidic isoferritins suppress the colony formation of U937 clonogenic cells, with lactoferrin and transferrin decreasing the release of growth factors from U937 cells which are needed to stimulate U937 colony formation, and lactoferrin and acidic isoferritins suppress the colony formation of WEHI-3 cells, with lactoferrin decreasing the release of growth factors from WEHI-3 cells which are needed to stimulate WEHI-3 colony formation. Speculation on the potential usefulness of these iron binding glycoproteins to control of disease progression is given in the discussion.