DIFFERENTIAL INDUCTION OF ADULT AND PETAL GLOBIN GENE-EXPRESSION IN THE HUMAN CML CELL SUBLINE KU-812F 33/

Various chemicals which are known to have positive effects on differen tiation of some erythroid cell lines were tested on a human chronic my elogenous leukemia cell line, KU-812F. Succinic acid, 5-azacytidine, d aunomycin, and hemin showed a positive effect. Among them, hemin and 5 -azacytidine were the most effective inducers for erythroid differenti ation of KU-812F cells. Dimethylsulfoxide, cytosine arabinofuranoside, and sodium n-butyrate showed no effect. In addition, subclone KU-812F /33 derived from the KU-812F cell line showed differential expression of the beta- and gamma-globin genes in the presence of either 2 mu M 5 -azacytidine or 40 mu M hemin. Hemoglobin synthesis in differentiated KU-812F/33 cells was analyzed by isoelectric focusing gel electrophore sis, and S1 mapping analysis of beta- and gamma-globin mRNA was perfor med. After treatment with 5-azacytidine, the beta-globin gene expressi on was predominantly enhanced (18.75-fold higher level of beta-globin mRNA). After treatment with hemin, the most notable increase was in th e gamma-globin gene expression (1.83-fold higher level of gamma-globin mRNA), while no increment of beta-globin was observed.