Cooperative effects of hemin and anthracyclines in promoting terminal erythroid maturation in K562 human erythroleukemia cells.

Simultaneous exposure to 30 microM hemin and 3 x 10(-8) M aclacinomycin (ACL) or mussetamycin for 6 days led to terminal differentiation of K562 cells. The number of hemoglobinized cells and the total hemoglobin content of cells treated with both ACL and hemin exceeded the sum of the corresponding values induced in response to each of these two agents when used alone. Although neither ACL nor hemin alone induced substantial morphological maturation, 40%-45% of cells treated with both agents developed the morphological characteristics of orthochromatophilic normoblasts, a level of maturation not previously reported for this highly malignant cell line. Subcloning of K562 cells that had been treated with both ACL and hemin in inducer-free plasma clots revealed a 50% decrease in the clonogenic potential of these cells, even though the cells in the original cultures were still growing at only a moderately decreased rate. Despite the apparent terminal maturation of K562 cells induced with both ACL and hemin, with an advanced level of morphologic maturation and hemoglobin synthesis accompanied by a loss of proliferative capacity, these cells remained incapable of producing beta-globin chains and hence hemoglobin A.