To identify regulators of IL-2 signaling, we performed genome-wide CRISPR-knockout screening in IL-2–dependent cells derived from a patient with adult T cell leukemia (ATL) and found enrichment of single guide RNAs targeting PRDM1, which encodes B lymphocyte–induced maturation protein 1 (BLIMP1). Here, PRDM1 is linked to adult T-cell leukemia/lymphoma.