IRF1 activation and target gene induction drive all-trans retinoic acid efficacy in acute promyelocytic leukemia with potential as a predictive indicator for cancer treatment
All-trans retinoic acid (ATRA) exhibits significant therapeutic potential in various cancers, most notably for its success in treating acute promyelocytic leukemia (APL) by promoting differentiation. Beyond differentiation, ATRA can also induce cell cycle arrest, growth inhibition, and immune modulation in both hematopoietic and non-hematopoietic malignancies. Despite these multifaceted effects, the mechanisms driving ATRA efficacy remain incompletely understood, which has hindered its application to other cancers. To investigate the molecular basis of the anti-tumor actions of ATRA, we performed detailed time-series transcriptome analyses to identify key regulatory factors involved in ATRA's early transcriptional responses. Furthermore, chromatin immunoprecipitation sequencing (ChIP-seq) and functional assays evaluated the role of the key regulator, IRF1, to determine how it drives ATRA efficiency. Overall design: ChIP-seq profiling of IRF1 in NB4 cells treat with ATRA for 4 hours and control.