Control of normal differentiation of myeloid leukemic cells. X. Glucose utilization, cellular ATP and associated...

Glucose utilization, energy metabolism and associated membrane changes, have been studied in D+ myeloid leukemic cells that can be induced to undergo cell differentiation to mature granulocytes by incubation with the appropriate conditioned medium (CM) and in D- myeloid leukemic cells that cannot be induced to differentiate to mature cells. Before incubation with CM, glycolysis and the glycolytic production of ATP were lower and the activity of the pentose cycle was higher in D+ than in D- cells. ATP depletion induced a higher degree of agglutination by concanavalin A in D- than in D+ cells, indicating a difference in their surface membrane. There were no detectable differences in the transport of glucose and the synthesis of sterols and fatty acids. After incubation with CM, the D+ cells, like normal granulocytes, showed a higher glycolysis, produced their ATP more through glycolysis than oxidative phosphorylation, became less dependent on the exogenous supply of glucose and oxygen and had a lower rate of sterol and fatty acid synthesis. The differentiating D+ cells also showed a change in their surface membrane resulting in an increased agglutinability without a change in ATP content and a stimulation of the pentose cycle by concanavalin A. These properties, which were not acquired by D- cells, were found before most of the D+ cells had differentiated to mature granulocytes. The data indicate, that the block in the ability of the D- cells to differentiate and the acquistion of the metabolic properties of normal granulocytes by differentiating D+ cells, were associated with differences in the organization of the cell surface membrane.