Patients with chronic lymphocytic leukemia (CLL) who are treated via monotherapy, such as ibrutinib and venetoclax, eventually relapse after several years due to resistance to treatment. Arnon Kater, MD, PhD of the University of Amsterdam, Amsterdam, Netherlands, discusses a gating strategy, originally proposed by Dr Nicholas Chiorazzi for predicting resistance in CLL patients. His strategy involves comparing the expression of anti-apoptotic molecules, such as BCL-xL and MCL-1, in cells that have recently migrated from the lymph node to the blood to those that have been remaining in the blood for a longer period. He explains that application of ibrutinib to CLL patients would reduce the difference in expression of anti-apoptotic molecules between these cells. However, in CLL patients who are resistant to monotherapy, an increase in the difference would be observed after this initial reduction. He believes that the pattern of expression of anti-apoptotic molecules may represent a marker for resistance in CLL patients.