(A) CD40^+ve CLL cells free of a survival niche (eg, in the circulation) constitutively expressing high levels of proapoptotic Bim-EL and low antiapoptotic Mcl-1, A1/BFl-1, and Bcl-xL successfully killed by therapeutic drugs. (B) Same cells receiving survival signals (here via CD154/stroma) down-regulate Bim-EL, up-regulate Mcl-1, A1/BFl-1, and Bcl-xL and are rendered resistant to therapeutic drugs. (C) Niche-protected CLL cells exposed to c-Abl kinase inhibitors reboot to niche-free levels of apoptosis regulators while restoring sensitivity to therapeutic drugs. Professional illustration by Paulette Dennis.