Leukemia cells and the cytokine network.

The cytokine network plays an important role in the growth and differentiation of normal and leukemic cells. Stimulation of this network, which has positive and negative regulators, results in the induction or inhibition of certain hematopoietic events. A cytokine can have multiple effects on various cell types, and combinations of cytokines with each other or with other exogenous substances produce more pronounced effects than any cytokine or agent individually. The mechanisms by which cytokines affect normal and leukemic cell growth and viability may vary depending on the target cell or the cytokine(s) in question. Diseases such as leukemia may result from abnormalities in the cytokine network or their receptors. Cytokines play a major role in leukemogenesis. Normally, hematopoietic cells require certain cytokines for their viability and growth. When the viability factors are withdrawn, apoptotic cell death naturally occurs. Prevention of programmed cell death by the abnormal production of a cytokine may release the cell from normal growth control leading to malignant transformation. Disregulation of genes for hematopoietic growth factors and their receptors may be one of the events that leads to leukemogenesis through an aberrant autocrine growth mechanism. However, cytokines have been used as therapeutic agents in various ways. Differentiation therapy has been widely investigated and proven effective in certain types of cancer. Gene therapy, where the cytokine cDNA is used to reduce tumorigenicity and/or increase immunogenicity is promising. Another kind of therapy using alkylated growth factors has been under focus. This review summarizes the actions and interactions of cytokines that are related to leukemic cell viability and growth. The use of cytokines as therapeutic agents is also discussed.