Disrupted signaling pathways in ABC-DLBCL. ABC-DLBCL is defined by multiple genetic alterations that fuel malignant transformation by sustaining constitutive NF-κB activity downstream of the BCR and TLR, while blocking terminal B-cell differentiation. Genes directly targeted by these lesions are shown in blue (inactivation) and red (deregulated expression/activity), and symbols at the bottom denote gain-of-function and loss-of-function events. Upstream inhibitors of the BCR, PI3K, and NF-κB signal transduction pathway have shown promising effects in early clinical trials involving ABC-DLBCL patients. Modified from Pasqualucci and Dalla-Favera¹³⁵  with permission.