Colocalization of MYD88 and DOCK8 in primary DLBCLs and schema of augmented proximal BCR signaling in MYD88^L265P/CD79B^Y196X DLBCLs. (A) Confocal images of MYD88:DOCK8 PLA signals in 2 representative C3 (MYD88^WT/CD79B^WT) and 2 representative C5 (MYD88^L265P/CD79B^Y196X) primary DLBCLs. Scale bar, 10 μm. (B) Quantification of PLA signals in primary DLBCLs. PLA puncta in 10 000 μm² areas from triplicate core biopsies from 6 C3 (MYD88^WT/CD79B^WT) and 4 C5 (MYD88^L265P/CD79B^Y196X) primary DLBCLs were scored. Violin plots, ∗∗P < .01. Asterisks represent P values in a Mann-Whitney test. (C) Physiologic signaling. CpG-induced TLR signaling augments PYK2 phosphorylation and phosphorylation of the proximal BCR kinases SYK and BTK. DOCK8 phosphorylation, shown in gray, was previously demonstrated.²⁹ (D) Oncogenic signaling. MYD88^L265P increases PYK2 and DOCK8 phosphorylation and phosphorylation of SYK and BTK. (E) Therapeutic targeting. DOCK8 depletion decreases SYK and BTK phosphorylation and is selectively antiproliferative and cytotoxic in MYD88^L265P/CD79B^Y196F cell lines. TLR pathway members are shown in red; BCR pathway members are shown in blue.