Mutant NPM1 marginally impacts ribosome footprint in acute myeloid leukemia cells

Combining RNA-seq, Ribo-seq and selective NPM1c degradation through dTAG-13, we explored for the first time the impact of NPM1c on ribosome footprint in the two available NPM1-mutated cell lines. Analysis of translatome showed that NPM1c only marginally impacts ribosome abundance and positioning on mRNA in NPM1-mutated cells. We performed ribosome footprint profiling and bulk RNA sequencing in two NPM1-mutated cell lines (i.e. OCI-AML3 and IMS-M2), engineered to express endogenous NPM1c fused to the FKBP(F36V) degron domain. Incubation of degron cells with the small compound dTAG-13 enables highly specific degradation of >85% of NPM1c within 4h.