Issues

Primary acute myeloid leukemia (AML) cells are notoriously difficult to culture, which remains a limitation in modeling the disease. In this issue, Kotini, Carcamo, Cruz-Rodriguez et al. demonstrate a large-scale approach to renewable propagation of human AML cells by reprogramming them into induced pluripotent stem cells (iPSC). With the exception of NPM1-mutant leukemia, all major genetic subtypes of the disease are amenable to reprogramming. When transplanted into mice, iPSC-derived AML cells give rise to serially transplantable leukemia mirroring immunophenotypes of the donor. These results suggest that leukemia is determined largely by the genetic lesions, as epigenetic factors were presumably erased by the reprogramming process. iPSC-AML grafts sustain multilineage hematopoiesis in vivo, currently unattainable with normal iPSC-derived hematopoietic stem and progenitor cells. The diverse range of AML-iPSC lines generated in this study is an important resource for further research in this field. For details, please see the article by Kotini, Carcamo, Cruz-Rodriguez et al. on page 318.