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.
Highlights
Apoptosis is a physiological cell suicide program that is essential for the regulation of development, the maintenance of homeostasis and the prevention of tumorigenesis
Evading the apoptotic program is one of the hallmarks of cancer and represents an important mechanism in clinical resistance to therapies [1,2]. This is true for chronic lymphocytic leukemia (CLL), a currently incurable condition that is clearly characterized by impaired apoptosis
The most encouraging clinical data have been obtained with flavopiridol and ABT263
Summary
Apoptosis is a physiological cell suicide program that is essential for the regulation of development, the maintenance of homeostasis and the prevention of tumorigenesis. Evading the apoptotic program is one of the hallmarks of cancer and represents an important mechanism in clinical resistance to therapies [1,2]. This is true for chronic lymphocytic leukemia (CLL), a currently incurable condition that is clearly characterized by impaired apoptosis. The development of therapeutic strategies that target apoptosis in CLL is a very important issue
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