INDUCTION OF DIFFERENTIATION OF THE HUMAN HISTIOCYTIC LYMPHOMA CELL-LINE U-937 BY RETINOIC ACID AND CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE-INDUCING AGENTS

Abstract

The monoblast-like human histiocytic lymphoma cell line, U-937, is induced to differentiate into monocyte-like cells by incubation with 0.1-1.0 .mu.M retinoic acid (RA). These induced cells are phagocytic, reduce nitroblue tetrazolium and show an increased hexose monophosphate shunt activity consistent with monocyte-like cells. Prostaglandin E, cholera toxin or dibutyryl cAMP, all inactive alone, increased markedly the extent of RA-induced differentiation of U-937. The intracellular level of cAMP is of importance for expression of the RA-induced effect. Responsiveness to RA seems to be limited to those leukemic myeloid cells blocked at a relatively late stage of maturation, like the promyelocytic HL-60 and the monoblast-like U-937 cell lines.