To further analyze the therapeutic potential of targeting LAG-3 in CLL, we analyzed the anti-leukemic effect of relatlimab, an anti-LAG-3 blocking antibody currently ongoing clinical trials in CLL (ClinicalTrials.gov Identifier: NCT02061761), as well as the potential underlying mechanisms leading to anti-tumor responses in patients with CLL. This evidence concerns the gene LAG3 and B-cell chronic lymphocytic leukemia.