The differentiation pathway of HL60 cells is a model system for studying the specific regulation of some myeloid genes.
During granulopoiesis, certain myeloid genes encoding products of azurophilic granules are specifically down-regulated. The myeloid specific enzyme myeloperoxidase belongs to this group of genes. It is responsible for the production of hypochlorous acid, a potent microbicidal agent which is involved in host defense. During induced differentiation of promyelocytic leukemic HL60 cells to granulocyte- or monocyte-like cells, myeloperoxidase RNA is depressed. We studied this depression process in more detail by limiting the exposure to the inducer phorbol 12-myristate 13-acetate to 24 h. During this time period, no significant decrease in cell number and cell viability could be observed. Analysis of these in vitro differentiated HL60 cells on the protein and RNA levels showed that they can be used under defined conditions as a cell system to study the specific depression of myeloid genes. Under the described conditions, both the transcriptional rate of the myeloperoxidase gene as well as the stability of its transcript was reduced.
Laboratory of Clinical and Experimental Research, University of Berne, Tiefenau Hospital, Switzerland.
R W
RW
Meier
T
T
Chen
S
S
Mathews
G
G
Niklaus
A
A
Tobler
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000470:Alkaloids / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D018821:CD18 Antigens; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006098:Granulocytes; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes; D009113:Muramidase / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D009195:Peroxidase / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D000470:Alkaloids; D015703:Antigens, CD; D018821:CD18 Antigens; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D003609:Dactinomycin; D009195:Peroxidase; D011493:Protein Kinase C; D009113:Muramidase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate