Apoptosis inducers in chronic lymphocytic leukemia

// Christian Billard 1,2 1 INSERM U 872, Centre de Recherche des Cordeliers, Equipe 18, Paris, France 2 Université Pierre et Marie Curie (UMRS 872), Paris, France. Correspondence: Christian Billard, email: // Keywords : CLL; impaired cell death program; apoptosis-targeted therapies; apoptosis inducers; Bcl-2 family proteins. Received : October 8, 2013 Accepted : November 18, 2013 Published : November 19, 2013 Abstract Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis and is still an incurable disease. Numerous apoptosis inducers have been described. These synthetic compounds and natural products (mainly derived from plants) display antileukemic properties in vitro and in vivo and some have even been tested in the clinic in CLL. They act through several different mechanisms. Most of them involve proteins of the Bcl-2 family, which are the key regulators in triggering the mitochondrial pathway of caspase-dependent apoptosis. Thus, the Mcl-1/Noxa axis appeared as a target. Here I overview natural and synthetic apoptosis inducers and their mechanisms of action in CLL cells. Opportunities for developing novel, apoptosis-based therapeutics are presented.