Lastly, to demonstrate that the BH3-mimetics are acting in an “on-target” mechanism, we have generated cell lines that are deficient in their ability to undergo apoptosis by genetically ablating the multi-domain apoptotic effectors, Bax and Bak. Thus, this panel of re-programmed B-ALL cells represents an important tool to assess the specificity and potency of BH3-mimetic small molecules both in culture and in vivo. This evidence concerns the gene BAK1 and acute lymphoblastic leukemia.