THE REGULATION OF GRANULOPOIESIS IN CHILDHOOD NEUTROPENIC DISORDERS AND ACUTE LEUKEMIA

The agar culture technic for the growth of human granulocytic colony forming cells (or CFC) from the bone marrow of patients may be used to study factors involved in the regulation of granulopoiesis. Bone marrow cells from 10 children with neutropenia were cultured in agar; the peripheral blood cells of these patients were also tested for their production of colony stimulating activity (CSA). It was observed that patients with aplastic anemia had decreased bone marrow CFC and decreased production of CSA. Other patients with neutropenia had normal CFC and increased CSA. This included 2 patients with “maturation arrest” neutropenia associated with type I(b) glycogen storage disease - a previously undescribed association. Leukemic children in relapse have decreased bone marrow CFC and peripheral blood CSA. However, when peripheral blood cells from certain neutropenic patients were used as feeder layers for bone marrow cells from leukemic children in relapse, a marked increase (up to fifty fold) in the number of granulocytic CFC was observed. It may be concluded that the defect in neutropenic conditions may be due to a decrease in CFC, or a decrease in CSA or “defective maturation”. The defect in granulopoiesis in the acute leukemia patients that we have studied was due to decreased CSA production which was corrected by factors in the peripheral blood cells of certain neutropenic patients.