cFos Mediates cAMP-Dependent Generation of ROS and Rescue of Maturation Program in Retinoid-Resistant Acute Promyelocytic Leukemia Cell Line NB4-LR1

Jean-Luc Carrier, Pasha Javadi, Emilie Bourrier, Céline Camus, Evelyne Ségal-Bendirdjian, Aïda Karniguian, Pierre Bobé
2012 PLoS ONE  
A determining role has been assigned to cAMP in the signaling pathways that relieve resistance to anti-leukemia differentiation therapy. However, the underlying mechanisms have not been elucidated yet. Here, we identify cFos as a critical cAMP effector, able to regulate the re-expression and splicing of epigenetically silenced genes associated with maturation (CD44) in retinoid-resistant NB4-LR1 leukemia cells. Furthermore, using RNA interference approach, we show that cFos mediates
more » ... ROS generation, a critical mediator of neutrophil maturation, and in fine differentiation. This study highlights some of the mechanisms by which cAMP acts to overcome resistance, and reveals a new alternative cFos-dependent pathway which, though nonexistent in retinoid-sensitive NB4 cells, is essential to rescue the maturation program of resistant cells.
doi:10.1371/journal.pone.0050408 pmid:23209736 pmcid:PMC3508928 fatcat:tfrp6ofi5rhwxftonwibzmkz2m