Signaling pathways activated by daunorubicin

The anthracycline daunorubicin is widely used in the treatment of acute non lymphocytic leukemia. The drug has, of course, been the object of intense b asic research, as well as preclinical and clinical study. As reviewed in th is article, evidence stemming from this research clearly demonstrates that cell response to daunorubicin is highly regulated by multiple signaling eve nts, including a sphingomyelinase-initiated sphingomyelin-ceramide pathway, mitogen-activated kinase and stress-activated protein/c-Jun N-terminal kin ase activation, transcription factors such as nuclear factor kappaB, as wel l as the Fas/Fas-ligand system. These pathways are themselves influenced by a number of lipid products (diacylglycerol, sphingosine-1 phosphate, and g lucosyl ceramide), reactive oxygen species, oncogenes (such as the tumor su ppressor gene p53), protein kinases (protein kinase C and phosphoinositide- 3 kinase), and external stimuli (hematopoietic growth factors and the extra cellular matrix). In light of the complexity and diversity of these observa tions, a comprehensive review has been attempted toward the understanding o f their individual implication (and regulation) in daunorubicin-induced sig naling. (C) 2001 by The American Society of Hematology.