PI3K inhibition may help overcome stroma-mediated resistance by increasing CLL cell priming. PB-derived CLL cells from 8 individual patients were cocultured for 24 hours ± StromaNKTert and ± 10μM CAL-101. (A) Mean CLL cell percent apoptosis as measured by annexin V/propidium iodide is depicted along with SEM for all 8 patient samples. In 2-way ANOVA analysis, stroma provided significant protection from spontaneous apoptosis in the absence of CAL-101. In the absence of stroma, CAL-101 induced significantly more apoptosis than control. In the presence of stroma, CAL-101 was also able to induce significantly more apoptosis than control. (B) A trend toward increased priming by BIM BH3 peptide was observed in stroma-exposed CLL cells treated with CAL-101 compared with controls (1-tailed P = .0749). (C-D) BAD BH3 peptide and ABT-737 used as a peptide both induced significantly increased mitochondrial depolarization in stroma-exposed CLL cells treated with CAL-101 compared with control (we predicted this result based on the results shown in panel A, and therefore 1-tailed P values were used: P = .0462 and P = .0468 for BAD and ABT-737, respectively).