Issues

Identifying seeds of relapse in the bone marrow samples of patients after allogeneic hematopoietic stem cell transplantation (HSCT) holds promise to predict or prevent relapse. However, this is technologically challenging as relapse-initiating cells are a rare subpopulation with only a few genetic lesions distinguishing them from their nonmalignant counterparts. On page 442, Penter and colleagues present a method to genetically distinguish cells in clinical samples by sequencing both nuclear and mitochondrial DNA while also capturing their phenotypes. Tracking mitochondrial DNA mutations increases the resolution and enables detection of rare relapse-fated clones in the complex mixture of post-transplantation bone marrow. The approach demonstrates coevolution of mitochondrial and somatic nuclear DNA mutations in acute myeloid leukemia and uncovers differences between physiologic and malignant cells within rare cell populations.