NORMAL NEUTROPHIL DIFFERENTIATION AND SECONDARY GRANULE GENE-EXPRESSION IN THE EML AND MPRO CELL-LINES

The EML and MPRO cell lints express a dominant negative retinoic add r eceptor alpha that causes a block at specific stages of myelopoiesis. The EML cell line is multipotent and gives rise to erythroid, lymphoid , and myeloid lineages depending on the presence of appropriate cytoki nes. The MPRO cell line is promyelocytic and undergoes neutrophilic di fferentiation when induced with all-trans retinoic acid in the presenc e of ganulocyte/macrophage colony-stimulating factor. Previous studies have shown that both of these cell lines undergo morphological differ entiation into neutrophils. In this study, we show that unlike other m odels of neutrophil differentiation such as NB4 and HL60, both EML and MPRO cell Lines undergo complete, normal granulocytic differentiation programs. Similar to HL60, MPRO and EML induce expression of CD11b/CD 18 and also exhibit downregulation of CD34 on differentiation. In cont rast to HL60 and NB4, EML and MPRO cell lines coordinately upregulate secondary granule transcripts for lactoferrin and neutrophil gelatinas e. Furthermore, we have confirmed previous observations that serum can induce a low level of differentiation in MPRO cells and that it is po ssible to grow these cells in serum-free medium, thereby eliminating t his effect. Based on these studies, it appears that these lines can se rve as a model for normal retinoic acid-induced neutrophil differentia tion and provide insight into the role of the retinoic acid-responsive pathway in normal and leukemic myelopoiesis.