{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:05:26Z","timestamp":1787731526683,"version":"build-2784847793"},"reference-count":48,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) with TP53 mutations is almost universally refractory to chemotherapy, molecular-targeted therapies, and hematopoietic stem cell transplantation, leading to dismal clinical outcomes. The lack of effective treatments underscores the urgent need for novel therapeutic strategies. Using genome-wide CRISPR\/Cas9 dropout screens in isogenic Trp53\u2013wild-type (WT) and Trp53-knockout mouse AML models, combined with transcriptomic and proteomic analyses of AML samples from mice and humans, we identify the XPO7-NPAT (exportin 7\u2013nuclear protein, coactivator of histone transcription) pathway as essential for TP53-mutated AML cell survival. In TP53-WT AML, XPO7 functions as a tumor suppressor by regulating the nuclear abundance of p53 protein, particularly when basal levels of functional p53 are high. However, in TP53-mutated AML, XPO7 drives leukemia proliferation by retaining NPAT, an XPO7-associated protein predominantly expressed in TP53-mutated AML, within the nucleus. NPAT depletion induces genome-wide histone loss, compromises genomic integrity, and triggers replication catastrophe in TP53-mutated AML cells. Notably, the analysis of publicly available AML data sets, primary AML samples, and single-cell intrapatient mRNA profiles further reveals elevated XPO7 and NPAT expression in TP53-mutated AML. Finally, we validate the XPO7-NPAT pathway as a critical driver of leukemia progression in vivo using patient-derived xenograft models of TP53-WT and TP53-mutant AML. Our study delineates key molecular mechanisms underlying TP53-mutated AML pathogenesis and identifies the XPO7-NPAT axis as a critical vulnerability in this refractory leukemia subtype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028918","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:48:06Z","timestamp":1761767286000},"page":"662-674","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["The XPO7-NPAT axis represents key vulnerabilities in\n                    <i>TP53<\/i>\n                    -mutated acute myeloid leukemia"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8576-3530","authenticated-orcid":false,"given":"Yuichiro","family":"Semba","sequence":"first","affiliation":[{"name":"1Division of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"},{"name":"2Department of 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