While acquired venetoclax resistance is explained in part by genetic mechanisms, such as the BCL2 p.G101V that reduces binding of venetoclax to BCL-2, these mutations are only observed in about half of the patients with CLL on long-term venetoclax therapy, and when these mutations do occur, they are often found at a low variant allele frequency (VAF) (4–6). Here, BCL2 is linked to B-cell chronic lymphocytic leukemia.