Specific PI3Kδ inhibition with CAL-101 induces CLL apoptosis and abrogates BCR-derived survival signals. (A) CLL cells were incubated in medium alone (control), medium containing 10 μg/mL of anti-IgM mAbs, or medium with anti-IgM mAbs and various concentrations of CAL-101. Displayed are representative contour plots that depict CLL cell viability after 48 hours and after post staining with DiCO6 and PI (horizontal and vertical axes, respectively). The viable cell population is characterized by bright DiCO6 staining and PI exclusion, and is gated in the bottom right corner of each contour plot. The percentage of viable cells is displayed above each of these gates. (B) The bar diagram represents the mean relative viabilities of CLL cells cultured in complete medium (control), or medium supplemented with 10 μg/mL of anti-IgM, or anti-IgM and various concentrations of CAL-101. Viabilities in CAL-101–treated samples were normalized to the viabilities of control samples at the respective timepoints (100%) to account for differences in spontaneous apoptosis in samples from different patients. Displayed are the means (± SEM) from 15 different patient samples, assessed after 24, 48, and 72 hours. CLL cell survival in the presence of anti-IgM mAbs was significantly inhibited by CAL-101, with P < .05, as indicated by the asterisks describing the comparison of results from each culture containing CAL-101 to the results from the culture containing anti-IgM alone.
