[Induced differentiation of the K562 leukemic cell line]

Hematopoietic cells undergo three major fates: proliferation, differentiation, and apoptosis. These processes are closely intertwined. Under normal circumstances, hematopoietic cell proliferation and cell death are carefully balanced. Induction of differentiation is associated with a loss of proliferative capacity, and cell death accompanies hematopoietic cell maturation. Leukemic transformations can be related to dysregulation of each of these processes. Considerable evidence supports the notion that leukemias are likely to arise from the disruption of the differentiation process of hematopoietic progenitors, which fail to give birth to blood cells with restricted phenotypes, as well as from diminished ability to undergo apoptosis. Main results supporting such mechanisms have been obtained from studying bone marrow and analyzing the differentiation process of the human K562 and HL-60 and mouse MEL leukemic cell lines. This paper reviews the current concepts of how understanding the mechanisms of action of differentiation-inducing agents may contribute to the development of less toxic strategies to control growth and apoptosis of human cancer cells. Furthermore, the identification of new approaches to induce erythroid differentiation and reactivate fetal globin genes is crucial for the development of potential therapeutic agents in hematological disorders, including beta-thalassemia. The natural/synthetic agents inducing differentiation of human erythroleukemia K562 cells are presented.