The effect of leukemic human serum on normal granulopoiesis

Acute lymphoblastic leukemia (ALL) in children is often characterized by defective granulopoiesis during initial and relapse stages of the disease, resulting in absolute neutropenia in vivo and in low or absent production of granulocyte-macrophage colonies in vitro. The purpose of this study was to determine if serum from leukemic children with ALL could inhibit normal granulopoiesis. Several concentrations of serum from 12 leukemic patients were mixed with normal bone marrow cells and co-cultured by the double layer agar technique. Also, serum from normal individuals and from ALL patients in remission and relapse was examined for inhibitors. Cultures without serum served as controls. The majority of ALL (initial, relapse and remission) and normal sera either stimulated or had no effect on colony formation. These groups also had similar percentages of inhibitory sera, with the exception of the somewhat higher levels of inhibition found in the remission group. Thus, ALL serum resembled normal serum in its effect on in vitro granulopoiesis at the committed granulocyte-macrophage stem cell level. It is therefore unlikely that inhibition of in vivo granulopoiesis at the committed level by serum inhibitors is responsible for ALL-associated neutropenia.