Deficiency in the apoptotic program is one of the hallmarks of chronic lymphocytic leukemia. Defective apoptosis mainly results from the constitutive activation of survival pathways, which leads to the transcription and overexpression of antiapoptotic factors. The latter include proteins of the Bcl-2 family and members of the IAP family. The strategy of inhibiting the expression or activity of these antiapoptotic factors has been extensively investigated. Conversely, upregulation of proapoptotic proteins, notably BH3-only members of the Bcl-2 family (capable of antagonizing their antiapoptotic counterparts) has also been consistently described. Either mechanism can promote apoptosis in chronic lymphocytic leukemia cells ex vivo. The present article recapitulates the mechanistic data and how they contribute to the development of therapeutic agents targeting apoptosis.
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