Defining the transcriptional control of pediatric AML highlights RARA as a superenhancer-regulated druggable dependency.

ABSTRACT: Somatic mutations are rare in pediatric acute myeloid leukemia (pAML), indicating that alternate strategies are needed to identify targetable dependencies. We performed the first enhancer mapping of pAML in 22 patient samples. Generally, pAML samples were distinct from adult AML samples, and MLL (KMT2A)-rearranged samples were also distinct from non-KMT2A-rearranged samples. Focusing specifically on superenhancers (SEs), we identified SEs associated with many known leukemia regulators. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort, and a RARA-associated SE was detected in 64% of the study cohort across all cytogenetic and molecular subtypes tested. RARA SE+ pAML cell lines and samples exhibited high RARA messenger RNA levels. These samples were spe

SUBMITTER: Perez MW 

PROVIDER: S-EPMC9153032 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature