Strategy to induce apoptosis and circumvent resistance in chronic lymphocytic leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) is characterised by the dependence on the overexpression of anti-apoptotic proteins to maintain their survival. Based on this biological context, a strategy for CLL therapy was proposed using inhibitors of transcription and translation to transiently reduce the short-lived survival proteins and induce cell death. This includes inhibitors of the cyclin-dependent kinases required for the activation of RNA polymerase II, as well as homoharringtonine and silvestrol, the natural compounds that inhibit translation. As their actions are independent of p53 or ataxia telangiectasia mutated (ATM) function, agents that act by such mechanisms are promising to overcome resistance to current CLL therapy. Further, the combination of inhibitors of transcription and translation, together with other approaches that interfere with the function of anti-apoptotic proteins, may initiate synergistic killing in CLL.