Figure 3. Different NUP98-fusion proteins regulate a common core of transcriptional targets.

(a) Schematic illustration of the experimental workflow to investigate NUP98-fusion protein-dependent transcriptional programs. NUP98-fusion-protein-driven leukemia cells were transplanted into secondary recipient mice. Mice were treated with Dox for 3 or 5 days after an initial engraftment phase of 15 days and leukemia cells were sorted from the bone marrow based on GFP/CD45.2 expression and gene expression was analyzed by RNA-seq (n ≥ 3). (b) Representation of dynamics of global gene expression changes after 3 and 5 days of Dox-induced NUP98-fusion-protein-repression. Each line represents the harmonized mean of the median expression of all genes within the cluster of distinct fusion-protein-driven cancer cells. Maximum/Minimum medians are indicated by the colored area. (c) GSEA indicating induction of myeloid differentiation upon fusion protein withdrawal. (d) Heatmap of 339 commonly up- and downregulated genes in all three NUP98-fusion-protein-driven models after 5 days of Dox-mediated fusion-protein repression (≥ 1.5-fold change, p < 0.01). (e) GSEA illustrating the enrichment of HOXA9 / MEIS1-target genes in cells expressing NUP98/NSD1.