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. 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.