Fig. 3.

Choline pathway dependency is linked to the activation of the PI3K pathway in the DLBCL cell line OCI-Ly1. (a) Deviation score vs. the effect differential illustrates the distribution and the number of compounds having enhanced susceptibility with (magenta) and without (blue) panobinostat pretreatment (left). Distribution and number of compounds within each category are denoted above the plot. Inset shows key targets representing high differential effect and deviation score (center). Network illustrating key interactions based on the targets of the 48 compounds identified to have greater effect than the CHKA inhibitor CK37 (right). Panobinostat pretreatment consisted in 10 nM exposure for 48 h. All compounds of the library were tested at 10 μM final concentration. (b) GI50 at 48 h of PI3K and MAPK inhibitors in OCI-Ly1 cells pretreated with vehicle (black dots) or 10 nM panobinostat (blue dots) for 48 h. (c) Viability (bottom) of OCI-Ly1 cells transfected with CHKA siRNA, pretreated with vehicle or 10 nM panobinostat, and exposed to 100 μM of the PI3K inhibitor AZD8186 for 24 h after pretreatment (top). (d) Viability (top) and caspase 3/7 activity (bottom) of OCI-Ly1 cells pretreated with vehicle or 10 nM panobinostat for 48 h, and then treated with 10 μM of the CHKA inhibitor CK37 (CHKAi) (left) or 100 μM of the PI3K inhibitor AZD8186 (right), with or without 100 μM phosphatidic acid (Ph. Acid) for the specified times. Data are represented as median ± SEM. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)