Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [SLAM-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 rapid changes just minutes after NPM1c degradation, we performed nascent mRNA sequencing (SLAM-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 treated with dTAG-13 for 15 to 180 minutes.