Elisa ten Hacken, PhD, Harvard Medical School, Boston, MA, discusses exciting updates from studies employing genetic engineering in mouse models of chronic lymphocytic leukemia (CLL), focusing on B-cell deprived controlled systems. Dr ten Hacken describes a study assessing how IKZF3 mutation affects cellular fitness during ibrutinib treatment. Other mutations currently being investigated in mouse models include those in the ribosomal proteins RPS15 and Cp53. The use of mouse models allows us to explore how different mutations affect disease outcomes and how they can be targeted therapeutically. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.