Together with our clinical partner, Dr. Kelly Faulk, we are performing correlative studies in conjunction with the Children’s Oncology Group Trial AALL2121. This work aims to better understand why some infants with B-ALL respond to menin inhibitors and some do not, by studying patient specimens as they undergo treatment (Figure). To better test hypotheses that come from analyzing patient specimens, we recently developed model system for MLL-rearranged pediatric B-ALL that enables studying the B-ALL as it develops in an immune-intact model system. Using this system, we are discovering factors that influence the process of lineage-switching, or the transition from B-ALL to AML. Lineage switching during relapse from CD19 directed therapies is a serious complication that limits the effectiveness of BiTE or CAR T cell therapy in these leukemia patients.