AFF1 and acute lymphoblastic leukemia: Much work has gone into developing targeted therapies, but even cancers with the same driver mutations show varied responses to therapy, along with significant transcriptional heterogeneity.24,44–46 Here, we have shown that enhancer heterogeneity is a common feature of KMT2A::AFF1 ALL, and could be a major driver of transcriptional heterogeneity between patients.