In line with this, we observed that HCV-derived B cells expressing IGHV1-69–encoded BCRs with CDR1 hotspot mutations upregulated, besides classical lymphoma drivers downstream of the BCR like MYC, NF-κB, MAPK, and NFAT pathway components such as CARD11, MALT1, RELB, PIM3, KRAS, MAP2K2, BCL3, and NFATC2. Here, MALT1 is linked to lymphoma.