Impaired production of GM-CSA in bone marrow and peripheral blood monocytes in two patients with severe congenital neutropenia.

The capacity of bone marrow and peripheral blood cells to stimulate colony formation by normal granulocyte-macrophage progenitor cells (CFU-GM) was investigated in two patients with severe congenital neutropenia using soft agar-gel culture techniques. In both patients, monocyte/macrophage-derived colony stimulating activity (GM-CSA) in conditioned medium was found to be significantly decreased compared to the control. Furthermore, the capacity of patients' unfractionated peripheral blood leukocytes to stimulate normal CFU-GM in overlayers, was also found significantly decreased. In contrast, the number of bone marrow and peripheral blood CFU-GM was within the normal range in both patients. Patients' CFU-GM showed a normal pattern of in vitro differentiation when they were stimulated by exogenous GM-CSA. These data indicate that in some cases of severe congenital neutropenia, monocyte/macrophage-derived GM-CSA may be impaired. Whether this abnormality plays some role in the regulation of granulopoiesis in these patients is unclear.