Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease.

ABSTRACT: Understanding the relative contributions of genetic and epigenetic abnormalities to acute myeloid leukemia (AML) should assist integrated design of targeted therapies. In this study, we generated induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature. Epigenetic reprogramming was therefore not sufficient to eliminate leukemic behavior. This approach also allowed us to study the properties of disti

SUBMITTER: Chao MP 

PROVIDER: S-EPMC5508733 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature