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Cancer patients with\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant hematopoietic stem and progenitor cells (HSPCs) \u2013 a condition termed clonal hematopoiesis (CH) \u2013 are at a particularly high risk for t-AML\/MDS. However, the pathogenesis of\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant t-AML\/MDS, especially the role of the\n                    <jats:italic>TP53<\/jats:italic>\n                    allelic state (i.e., mono- vs. biallelic), and its prognostic impact in AML\/MDS have remained only poorly understood. We developed novel in vitro and in vivo mouse models to investigate how mono- or biallelic\n                    <jats:italic>Trp53<\/jats:italic>\n                    mutations influence clonal expansion and leukemic progression from CH to t-AML\/MDS. While HSPCs with monoallelic\n                    <jats:italic>Trp53<\/jats:italic>\n                    mutations gain clonal fitness but retain their genomic integrity under chemo- or radiation therapy, biallelic\n                    <jats:italic>Trp53<\/jats:italic>\n                    mutations result in genomic instability and are essential for leukemic transformation. Moreover, we provide proof of concept that non-mutational p53 inactivation, such as\n                    <jats:italic>MDM2<\/jats:italic>\n                    overexpression, can replicate the effects of biallelic\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations, providing a possible explanation for cases of\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant AML\/MDS that retain one wild-type\n                    <jats:italic>TP53<\/jats:italic>\n                    allele. Our findings elucidate the pathogenesis of\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant t-AML\/MDS and support the classification of biallelic\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant AML\/MDS as distinct clinical entities.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02839-5","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T07:44:12Z","timestamp":1765957452000},"page":"279-292","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The pathogenesis of therapy-related myeloid neoplasms from TP53-mutant clonal hematopoiesis"],"prefix":"10.1038","volume":"40","author":[{"given":"Jonas","family":"Fullin","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-4893","authenticated-orcid":false,"given":"Ebru","family":"Top\u00e7u","sequence":"additional","affiliation":[]},{"given":"Karolina A.","family":"Zieli\u0144ska","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0846-8508","authenticated-orcid":false,"given":"Roman R.","family":"Schimmer","sequence":"additional","affiliation":[]},{"given":"Nancy","family":"Klemm","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0681-4265","authenticated-orcid":false,"given":"Christian","family":"Koch","sequence":"additional","affiliation":[]},{"given":"Francisco","family":"Caiado","sequence":"additional","affiliation":[]},{"given":"Melissa","family":"Lock","sequence":"additional","affiliation":[]},{"given":"Cyril","family":"Doerdelmann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-3326","authenticated-orcid":false,"given":"Marco M.","family":"B\u00fchler","sequence":"additional","affiliation":[]},{"given":"Joelle","family":"Tchinda","sequence":"additional","affiliation":[]},{"given":"Kari J.","family":"Kurppa","sequence":"additional","affiliation":[]},{"given":"Lubor","family":"Borsig","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-795X","authenticated-orcid":false,"given":"Philip H.","family":"Jones","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3847-8133","authenticated-orcid":false,"given":"Massimo","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Markus G.","family":"Manz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-0957","authenticated-orcid":false,"given":"Steffen","family":"Boettcher","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"2839_CR1","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","volume":"371","author":"S Jaiswal","year":"2014","unstructured":"Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. 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