Despite the high response rates seen with venetoclax treatment in patients with heavily pre-treated chronic lymphocytic leukemia (CLL), disease in most patients will eventually progress. Piers Blombery, MBBS, FRCPA, FRACP, of the University of Melbourne and Peter MacCallum Cancer Centre, Melbourne, Australia, discusses a new recurrent BCL2 mutation (Gly101Val) appearing in a cohort of CLL patients who progress following venetoclax treatment. Speaking from the American Society of Hematology (ASH) 2018 Annual Meeting and Exposition in San Diego, CA, Dr Blomery reveals how this provides a new look into the pathobiology of venetoclax resistance, offering a potential biomarker to predict clinical relapse.