Human myeloid leukaemic cell interactions in vitro with normal myeloid colonies

Abstract

To determine whether myeloid leukaemic cells could inhibit normal myeloid colony formation, leukaemic cells at concentrations ranging from 0.5 to 8 X 10(6)/ml were co-cultured in agar but separated by a 1 ml underlayer from 10(5) low-density (less than 1.077 g/ml) nonadherent normal marrow cells. Inhibition of normal-marrow myeloid colony formation occurred regularly at high cell concentrations (8 X 10(6)) at a leukaemic:normal cell ratio of 80:1. This suppression persisted with addition of indomethacin (10(-6)M). On the other hand, both low leukaemic cell numbers and irradiated leukaemic cells frequently stimulated normal colony growth. No inhibitor of colony growth could be detected in leukaemic-conditioned media, and absorption of colony-stimulating activity (CSA) with leukaemic cells improved CSA activity. These experiments point to the difficulty in unravelling the effect of leukaemic cells on normal haemopoiesis (both inhibitory and stimulatory) by in vitro agar culture.

Endogenous Regulation of Macrophage Proliferative Expansion by Colony-Stimulating Factor-Induced Interferon

“…Since the original proposal of Kurland and his co-workers (5,(9)(10)(11) that production of series E prostaglandins by CSFinduced macrophages has a negative reg-ulatory role, evidence has been presented that macrophages within the marrow can act as suppressors of the myelopoietic response (17)(18)(19). Our results confirm the presence of an adherent regulatory cell that functions as a negative feedback inhibitor in a manner similar to that described by Kurland et al; that is, exposure to a macrophage-active CSF results in the -production of an inhibitor of CSF-induced proliferation of committed macrophage precursors.…”