Breaking through BCL-2 inhibition in CLL

In this issue of Blood, Blombery and colleagues have identified multiple novel somatic mutations in BCL-2 occurring concurrently with the recently reported Gly101Val BCL-2 resistance mutation in patients with chronic lymphocytic leukemia (CLL) receiving venetoclax.(1) Their study demonstrates that, in addition to functional resistance mechanisms such as aberrant expression of other antiapoptotic proteins, multiple acquired resistance mutations in BCL-2 can occur in different CLL cells in a single patient.