Patient-specific enhancers in genetically uniform leukemias.

In this issue of Blood, Smith et al tackle the question of how cancers with low mutation burden can exhibit profoundly diverse transcriptional signatures and clinical phenotypes. The investigators discover that tumor cells from patients with acute lymphoblastic leukemia (ALL) harboring the KMT2A::AFF1 rearrangement exhibit a highly heterogeneous transcriptional landscape, which is dynamically shaped by the presence of unique enhancers that are patient-specific (see figure).