Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence.

ABSTRACT: Patients with acute myeloid leukemia (AML) frequently relapse after chemotherapy, yet the mechanism by which AML reemerges is not fully understood. Herein, we show that primary AML cells enter a senescence-like phenotype following chemotherapy in vitro and in vivo. This is accompanied by induction of senescence/inflammatory and embryonic diapause transcriptional programs, with downregulation of MYC and leukemia stem cell genes. Single-cell RNA sequencing suggested depletion of leukemia stem cells in vitro and in vivo, and enrichment for subpopulations with distinct senescence-like cells. This senescence effect was transient and conferred superior colony-forming and engraftment potential. Entry into this senescence-like phenotype was dependent on ATR, and

SUBMITTER: Duy C 

PROVIDER: S-EPMC8178167 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature