As another example, a patient with chronic lymphocytic leukemia responded to anti-CD19 CAR-T cell therapy only upon receiving a second dose of CAR-T cells, and the anti-tumor efficacy was attributed in large part to clonal expansion of a particular CAR-T cell that lacked any functional copy of TET2 (the patient had a congenital mutation in one copy of TET2, and the CAR transgene was randomly inserted into the other copy, thereby generating a double-knockout) [77]. This evidence concerns the gene TET2 and B-cell chronic lymphocytic leukemia.