Retinoic acid-induced monocytic differentiation of HL60/MRI, a cell line derived from a transplantable HL60 tumor

Abstract

The human promyelocytic leukemia cell line HL60 differentiates to either granulocytes or monocytes/macrophages when induced with various chemicals and lymphokines. Retinoic acid (RA) induces HL60 to differentiate to granulocyte-like cells. However, HL60/MRI cells, derived from a transplantable HL60 tumor established in athymic nude mice, differentiate to monocytoid cells when cultured with RA in vitro. HL60/MRI induced with RA are monocytes based on morphology and the expression of markers and functions specific for monocytes such as: the OKM5 monocyte-specific antigen, nonspecific esterase activity, and adhesiveness. HL60/MRI is much more sensitive to RA than is HL60. Thus, the RA concentrations that induce 50% differentiation are 0.41 nM for HL60/MRI and 37 nM for HL60, and maximum differentiation occurs at 2 days for HL60/MRI and at 4 days for HL60. While RA induces HL60/MRI to monocytoid cells, other inducers of granulocytic differentiation of HL60, such as dimethyl sulfoxide and hexamethylene bisacetamide, induce HL60/MRI to granulocytes. Furthermore, 12-O-tetradecanoylphorbol-13-acetate induces both HL60 and HL60/MRI to macrophage-like cells. The isozyme phenotypes of HL60/MRI and HL60 are identical. Cytogenetic analysis of HL60/MRI indicates that many of its normal chromosomes are triploid and that it has five abnormal chromosome markers, M1-M5, three of which, M1-M3, are seen also in HL60. This unique cell line, HL60/MRI, may be useful for studying the event(s) triggering differentiation of myelomonocytic cells and the mechanism of action of RA.