Granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by a reduction in levels of inositol lipid-derived second messengers

Abstract

We have labeled HL60 human promyelocytic leukemia cells to isotopic equilibrium with [1-3H]glycerol or myo-[2-3H]inositol in order to determine the molar ratios of glycerol lipid species and of inositol-containing lipids and water-soluble compounds, respectively. The cellular content of diacylglycerol (DAG) and of inositol phosphates (IPs) declined significantly following induction of granulocytic differentiation by dimethylsulfoxide. Changes in levels of these compounds preceded the withdrawal of induced cells from the proliferative cycle. Because DAG and IPs are important biochemical second messengers in the regulation of cell proliferation, these observations are consistent with the hypothesis that the constitutive generation of these compounds may contribute to the deregulated proliferation of HL60 cells and that their reduced production may be associated with the cessation of proliferation which precedes morphological differentiation of these cells.