{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:26:37Z","timestamp":1789104397695,"version":"build-2803163510"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Childhood cancer survivors are confronted with various chronic health conditions like therapy-related malignancies. However, it is unclear how exposure to chemotherapy contributes to the mutation burden and clonal composition of healthy tissues early in life. Here, we studied mutation accumulation in hematopoietic stem and progenitor cells (HSPC) before and after cancer treatment of 24 children. Of these children, 19 developed therapy-related myeloid neoplasms (t-MN). Posttreatment HSPCs had an average mutation burden increase comparable to what treatment-na\u00efve cells accumulate during 16 years of life, with excesses up to 80 years. In most children, these additional mutations were induced by clock-like processes, which are also active during healthy aging. Other patients harbored mutations that could be directly attributed to treatments like platinum-based drugs and thiopurines. Using phylogenetic inference, we demonstrate that most t-MN in children originate after the start of treatment and that leukemic clones become dominant during or directly after chemotherapy exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Our study shows that chemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, whereas in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-22-0120","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T08:34:07Z","timestamp":1657787647000},"page":"OF1-OF14","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Elevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0012-7816","authenticated-orcid":false,"given":"Eline J.M.","family":"Bertrums","sequence":"first","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."},{"name":"3Department of Pediatric Oncology, Erasmus Medical Center \u2013 Sophia Children's Hospital, Rotterdam, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4001-5605","authenticated-orcid":false,"given":"Axel K.M.","family":"Rosendahl Huber","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5665-3711","authenticated-orcid":false,"given":"Jurrian K.","family":"de Kanter","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-4046","authenticated-orcid":false,"given":"Arianne M.","family":"Brandsma","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-707X","authenticated-orcid":false,"given":"Ana\u00efs J.C.N.","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2416-7492","authenticated-orcid":false,"given":"Mark","family":"Verheul","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7760-879X","authenticated-orcid":false,"given":"Marry M.","family":"van den Heuvel-Eibrink","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"4Utrecht University, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-7250","authenticated-orcid":false,"given":"Rurika","family":"Oka","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3329-1185","authenticated-orcid":false,"given":"Markus J.","family":"van Roosmalen","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-188X","authenticated-orcid":false,"given":"Hester A.","family":"de Groot-Kruseman","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-8268","authenticated-orcid":false,"given":"C. Michel","family":"Zwaan","sequence":"additional","affiliation":[{"name":"3Department of Pediatric Oncology, Erasmus Medical Center \u2013 Sophia Children's Hospital, Rotterdam, the Netherlands."},{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4030-3228","authenticated-orcid":false,"given":"Bianca F.","family":"Goemans","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-2836","authenticated-orcid":false,"given":"Ruben","family":"van Boxtel","sequence":"additional","affiliation":[{"name":"1Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands."},{"name":"2Oncode Institute, Utrecht, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2022,7,14]]},"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-22-0120\/3180365\/cd-22-0120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-22-0120\/3180365\/cd-22-0120.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T08:34:08Z","timestamp":1657787648000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/doi\/10.1158\/2159-8290.CD-22-0120\/707008\/Elevated-Mutational-Age-in-Blood-of-Children"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-22-0120","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.22541080","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541077","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.22541077.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6549550.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541080.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6549550","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}