Relapse occurring after standard and emerging therapies remains hard to cure. Only about half of patients who relapse after ALL relapse will survive their leukemia. We use patient samples and single-cell studies to identify ALL cells predictive of future relapse and then interrogate these cells as to why they were treatment resistant in the first place. Recent work has identified cells resistant to the therapeutic workhorse in ALL, glucocorticoids, and identified dasatinib as an additional agent to overcome this resistance (Sarno et al., Nat Comm 2023).
In the case of patients receiving chimeric antigen receptor T (CAR T) cells for relapsed leukemia, we are discovering cells that are prone to loss of the CAR target, CD19 or CD22 and have identified key transcription factors that lead to loss of this target, leading to antigen loss relapse. These studies will help us better predict what patients are at risk of antigen escape relapse and determine better treatment paradigms for these patients.