Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [PRO-seq]

We use an endogenously degrader tagged NPM1c leukemia cell line that allows rapid small molecule induced degradation to show that NPM1c occupies specific chromatin targets in AML. Overall design: To investigate the changes in transcriptional activity and potential defects in initiation versus elongation of RNA polymerase II, we performed precisiojn run on sequenign (PRO-seq) in NPM1 mutant leukemia cell line (OCI-AML3-NPM1c-FKBP12) in which only the mutant allele of NPM1 is modified to produce an endogenously tagged version of NPM1c that has an FKBP12 tag. Treatment with dTAG-13 for 30 or 60 minutes was used to determine transcriptional changes after NPM1c degradation.