In clinical trials, ABT-199 has yielded impressive results in the treatment of relapsed/refractory CLL.56 This apparent ABT-199 resistance is most likely attributable to high levels of Bcl-XL expression (Supplementary Figure 8a), which in CLL has been linked to a 1000-fold reduction in ABT-199 sensitivity.46 In contrast to ABT-199 monotherapy, PI3Kδi:ABT-199 combination therapy reduced in vivo leukemic burden by 95% in comparison to vehicle controls. This evidence concerns the gene BCL2L1 and B-cell chronic lymphocytic leukemia.