Idelalisib bypasses microenvironment-derived resistance to venetoclax. (A) FL cells from monocultures (FL) or FL-FDC and FL-Mϕ cocultures treated with or without idelalisib (500 nM, 24 hours) were permeabilized and incubated for 1 hour with 10 μM venetoclax fixed/stained for intracellular cytochrome C and evaluated by flow cytometry as a read-out of apoptosis priming (n = 13). (B) Cell viability (AnnexinV⁻/7AAD⁻) was assessed in FL cells from FL-FDC and FL-Mϕ with and without idelalisib (500 nM) and with and without venetoclax (10 nM) after 72 hours of treatment (n = 8). (C) FL cells from monocultures or FL-FDC cocultures (n = 3) with or without idelalisib (IDELA, 500 nM, 3 hours) were lysed, and the phosphorylation of BAD at Ser112 and Ser136 was analyzed by Peggy Sue simple Western blotting and quantified by densitometry. Images from a representative case (FL3) are shown. (D) Rational of venetoclax PI3Kδ combined therapy in FL. *P < .05, **P < .01, ***P < .001.