Changes in insulin binding activity during myeloid differentiation.

Abstract

Insulin binding activity and its changes in relation to terminal differentiation were studied in the HL60 human promyelocytic cell line, and in myeloid cells from both normal bone marrow and chronic myeloid leukemia (CML) patients. After treatment with dimethylsulfoxide, the HL60 line began to differentiate into more mature myeloid cells. Treated and untreated HL60 cells were found to possess specific insulin receptors with characteristics similar to those of monocytes and granulocytes. Dimethylsulfoxide induced a progressive decrease in insulin binding, parallel to the increase in the proportion of differentiated cells. Myeloid cells from CML patients were used to study insulin binding characteristics during spontaneous differentiation. They were separated on Ficoll Hypaque into a light fraction, containing mostly undifferentiated cells, and a dense fraction, containing mostly granulocytes, with similar specific insulin receptor characteristics. Insulin binding capacity, however, was twice as high in the light fraction. To compare binding activity during normal and leukemic myeloid differentiation, cells from normal bone marrow and CML peripheral blood were fractioned by BSA density gradient into enriched fractions of one predominant cell type. Insulin binding decreased in the course of both differentiations. These findings indicate that leukemic immature myeloid cells possess a high number of specific insulin receptors, and that insulin binding decreases during both spontaneous and chemically induced terminal differentiation.