Genes Reprogramming During ATRA-induced Differentiation of Acute Promyelocytic Leukemia Cells

The therapeutic and preventive activities of retinoids in cancer are due to their ability to modulate the growth, differentiation, and survival or apoptosis of cancer cell. An acute promyelocytic leukemia cell line AP-1060 presents an abrupt response to all-trans retinoic acid (ATRA) which depends on its mutant PML/RAR alpha. Microarray analysis of 9265 sequences demonstrated a complex cascade of reprogramming of AP1060 upon treatment with ATRA characterized by the differential expression of gene sets between induced (100nM ATRA) and sub-induced (10nM ATRA) cells. Among 1550 modulated genes by ATRA, 47% shown differential expression. A number of the small G-protein family was extensively involved in this reprogramming. The early up-regulated IL1 and down-regulated its angonistor may initiate the apoptosis pathway mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Seven in absentia (Drosphila) homologies (SIAH-1, 2, and 3) considered as the inducers of apoptosis were repressed. Thus, a balanced functional network seem emerge and contribute to ATRA inducing differentiation based on the uniquely biologic and molecular characters of AP1060. [Yiwu Sun, Kafeel I Muhammad, Neal Hakimi. Genes Reprogramming During ATRA-induced Differentiation of Acute Promyelocytic Leukemia Cells. Life Science Journal 2011;8(4):1058-1067]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 132