KLHL14 is a tumor suppressor in ABC DLBCL. (A) Percentage of KLHL14 mutations in DLBCL patients (n = 574) and in patients with lymphoid malignancies (n = 5,692). (B) Schematic representation of KLHL14 domain, organization, and mutations in DLBCL. (C) Western blot analysis of whole cell lysates, from TMD8 cells retrovirally transduced with cDNAs encoding an empty vector (EV), hemagglutinin (HA)-tagged version of KLHL14 wild-type (KLHL14WT) or eight lymphoma-derived KLHL14 mutant isoforms. Cells were treated with 50 μg/mL of cycloheximide (CHX) for the indicated time points before cell lysis. (D) FACS analysis of TMD8, RIVA, and OCI-LY10 cells retrovirally transduced with cDNAs encoding EV, KLHL14WT, or eight KLHL14 mutant isoforms along with the LYT2 (mouse CD8a) surface marker. The percent viable LYT2+ (KLHL14 expressing) cells was analyzed on the indicated posttransduction days. Error bars represent SD of triplicates, and data are representative of three independent experiments.