GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE264nnn/GSE264594/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264594GEOGSEfalseThe XPO7-NPAT axis represents key vulnerabilities in TP53-mutated acute myeloid leukemia (ATAC-Seq)Mutation of TP53, a tumor suppressor in cancer, is common and leads to extremely poor prognosis. To identify vulnerabilities in TP53-mutated tumors, we performed genome-wide CRISPR/Cas9 screens using isogenic Trp53 wild-type and knockout mouse acute myeloid leukemia (AML) lines. Here, we show that histone gene regulation governed by the XPO7-NPAT pathway is essential for survival of TP53-mutated AML cells. In TP53 wild-type cells, XPO7 enhances p53 nuclear localization and functions as a tumor suppressor, but in TP53-mutated cells, XPO7 promotes cell proliferation by retaining NPAT, a histone gene activator, in the nucleus. NPAT depletion led to genome-wide histone loss, enhancing vulnerability to genotoxic stress. Human AML cases show predominant expression of XPO7 and NPAT when TP53 is mutated, suggesting a potential therapeutic vulnerability.2026/04/22GSE264594GSM8223518GSM8223519GSM8223511GSM8223512GSM8223513GSM8223514GSM8223515GSM8223516GSM822351721626264594Mus musculus