Erythroid differentiation and modulation of c-myc expression induced by antineoplastic drugs in the human leukemic cell line K562.
The human leukemia cell line K562 expresses constitutively high levels of c-myc mRNA and can be induced to differentiate along the erythroid lineage. Treatment of K562 cells with the antineoplastic drugs 1-beta-D-arabinofuranosylcytosine and daunomycin causes differentiation into hemoglobin-producing cells. The differentiation process is associated with an early block of cellular proliferation occurring during the first 24 h of treatment. RNA synthesis is progressively reduced to 20 to 30% of the control levels after 3 days of exposure to the drugs. Dot and Northern blot analyses were performed to evaluate the levels of c-myc or globin mRNA during the differentiation of K562. Daunomycin and 1-beta-D-arabinofuranosylcytosine, despite their distinct chemical nature, induced similar modulation of mRNA levels. Globin mRNA did not change during the first 24 h of culture and began to increase after 48 h of treatment with drugs, reflecting the kinetic of appearance of hemoglobin-producing cells. In contrast, a transient decrease of c-myc mRNA was observed after the first 24 h of drug treatment, followed by a return to normal levels of c-myc mRNA after 48 h of treatment. Thus, the expression of c-myc mRNA in K562 did not reflect their proliferative activity nor their stage of differentiation. We speculate that the transient down-regulation of c-myc mRNA may be an initial event in the erythroid differentiation of K562.
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D003630:Daunorubicin / Q000494:pharmacology*; D004912:Erythrocytes / Q000473:pathology*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D003561:Cytarabine; D005914:Globins; D004247:DNA; D003630:Daunorubicin