Schematic of key survival pathways at work in the HRS malignant cell. Novel findings of pathway dysregulation reported in Tiacci et al are highlighted (green crosses and red arrows), along with the established REL and P53 abnormalities already known from the literature. LMP1 signaling is likely a key survival pathway in EBV positive disease, while signaling through TNFRSF pathway may provide redundancy for this pathway in EBV negative disease, along with the JAK/STAT and PI3K/MTOR pathways. Professional illustration by Marie Dauenheimer.